Orwik

Immunity in the elderly: the role of the thymus.

Adjustments to lifestyle including social and medical changes have led to human populations having increased longevity in many countries, producing shifts in the population demographics. Approximately half of the increase in the world's population by... expand abstract 2050 may be accounted for by the prolonged survival of those over the age of 60. It is possible to age in relatively good health, but this is rare and for the majority of individuals, growing old is associated with functional impairment, an increased risk of developing a degenerative condition, an increased susceptibility to disease and an increased risk of death. The ageing human population is one of the most urgent challenges facing us today. Changes in the immune system are considered to have a critical role in the decline seen with age, since many infectious diseases may no longer kill an individual, but may contribute to more subtle overall changes. So the impact of infections in older individuals should not be measured only in terms of direct mortality rates, but also by their contribution to the 'indirect' mortality rate and to changes in the quality of life. Taking a pragmatic approach, we need to understand the drivers for immune decline if we are to consider intervening therapeutically in this process. One of the central drivers to this process is age-linked atrophy of the thymus and reversal of this process may have a considerable role in reversing immune decline. collapse abstract

Influenza control in the 21st century: Optimizing protection of older adults.

Older adults (> or =65 years of age) are particularly vulnerable to influenza illness. This is due to a waning immune system that reduces their ability to respond to infection, which leads to more severe cases of disease. The majority ( approximately... expand abstract 90%) of influenza-related deaths occur in older adults and, in addition, catastrophic disability resulting from influenza-related hospitalization represents a significant burden in this vulnerable population. Current influenza vaccines provide benefits for older adults against influenza; however, vaccine effectiveness is lower than in younger adults. In addition, antigenic drift is also a concern, as it can impact on vaccine effectiveness due to a mismatch between the vaccine virus strain and the circulating virus strain. As such, vaccines that offer higher and broader protection against both homologous and heterologous virus strains are desirable. Approaches currently available in some countries to meet this medical need in older adults may include the use of adjuvanted vaccines. Future strategies under evaluation include the use of high-dose vaccines; novel or enhanced adjuvantation of current vaccines; use of live attenuated vaccines in combination with current vaccines; DNA vaccines; recombinant vaccines; as well as the use of different modes of delivery and alternative antigens. However, to truly evaluate the benefits that these solutions offer, further efficacy and effectiveness studies, and better correlates of protection, including a precise measurement of the T cell responses that are markers for protection, are needed. While it is clear that vaccines with greater immunogenicity are required for older adults, and that adjuvanted vaccines may offer a short-term solution, further research is required to exploit the many other new technologies. collapse abstract

B-cell responses to vaccination at the extremes of age.

Infants and the elderly share a high vulnerability to infections and therefore have specific immunization requirements. Inducing potent and sustained B-cell responses is as challenging in infants as it is in older subjects. Several mechanisms to expl... expand abstractain the decreased B-cell responses at the extremes of age apply to both infants and the elderly. These include intrinsic B-cell limitations as well as numerous microenvironmental factors in lymphoid organs and the bone marrow. This Review describes the mechanisms that shape B-cell responses at the extremes of age and how they could be taken into account to design more effective immunization strategies for these high-risk age groups. collapse abstract

Reversal of age-associated thymic atrophy: treatments, delivery, and side effects.

Our ability to survive infectious agents depends on making adequate immune responses, but as we get older our thymus atrophies. Production and export of T cells bearing new antigen receptor specificities to the peripheral T cell pool declines and res... expand abstractults in shrinkage of the repertoire. Other changes in the peripheral T cell pool include an increase in cells moving closer to their replicative limit. Age related immune dysfunction, evident through the increased susceptibility to infection, follows these changes. Improvement in immune function in the elderly may require us to rejuvenate the immune system starting first with reversing the atrophy seen in the thymus. This has been achieved experimentally with interleukin 7, growth hormone, growth hormone secretagogues, keratinocyte growth factor or through chemical or surgical castration. The widespread use of one or more of these treatments will depend upon their effectiveness, their ease of delivery and the extent of any side effects. collapse abstract

Thymic output, ageing and zinc.

The role of the thymus is vital for orchestration of T-cell development and maturation. With increasing age the thymus undergoes a process of involution which results in a reduction in thymic size, function and output. Until relatively recent it was ... expand abstractnot feasible to accurately measure the magnitude of age-related loss of thymic function. With the discovery of T-cell receptor excision circles (TRECs), which are the stable by-products of the newly generated T-cells, it is now possible to quantitatively measure the extent of thymic output. This review examines the available data on immune function and zinc deficiency and places them in the context of the aims of the ZINCAGE project which include the evaluation of the role played by zinc in maintaining thymic output in healthy elderly individuals. collapse abstract

Long-term effects of perinatal nutrition on T lymphocyte kinetics in young Gambian men.

BACKGROUND: Nutritional status is highly dependent on season in countries such as The Gambia. In a rural Gambian setting, individuals born during periods of seasonal nutritional deprivation ("hungry seasons") are susceptible to mortality from infecti... expand abstractous diseases in adult life. OBJECTIVE: We investigated the hypothesis that impaired immunocompetence in those born in the hungry season results from an underlying defect in immunologic memory, similar to the immunosenescence of old age, which is likely to be reflected in the phenotype and kinetics of T lymphocytes in young adults. DESIGN: T cell phenotype in terms of CD3, CD4, CD8, CD45RA, and CD45R0 expression and in vivo dynamics measured by stable isotope labeling of T cell subsets combined with gas chromatography-mass spectrometry and frequency of T cell receptor excision circles were measured in 25 young (18-24-y-old) Gambian men. Thirteen of these 25 men were exposed to perinatal malnutrition as defined by birth season and birth weight. RESULTS: In persons born in the hungry season with low birth weight, no differences in the proportions of memory or naive T cells were found. Kinetic analysis showed higher proliferation rates in memory (CD45R0(+)) subsets of T cells than in naïve (CD45R0(-)) cells, which is consistent with previous studies, but no evidence was found for an effect of birth weight or season on T lymphocyte proliferation and disappearance rates. No significant correlations were found between in vivo T cell kinetics and frequency of T cell receptor excision circles. Only absolute numbers of granulocytes were elevated in those born in the nutritionally deprived season. CONCLUSION: In healthy young Gambian men, T lymphocyte homeostasis is extremely robust regardless of perinatal nutritional compromise. collapse abstract

Early immunological development and mortality from infectious disease in later life.

In rural Gambia the risk of mainly infection-related mortality is 10-fold higher for adults born in the nutritionally-debilitating 'hungry' season, suggesting that immune function may be compromised by events early in life. The current programme of r... expand abstractesearch focuses on the biological mechanisms underlying this hypothesis, exploring early-life environmental influences on immune development and the long-term functional consequences these influences may have. Results obtained to date show that thymus development during infancy is critically sensitive to environmental exposures, with smaller thymuses observed in the hungry season. Measurement of the frequency of T-cell receptor excision circles indicate that thymus function is also sensitive to seasonal influences, with further studies implicating variations in breast-milk IL-7 as a possible mediator of these effects. Studies in adults have shown that size at birth is positively correlated with antibody responses to vaccination with polysaccharide antigens, thus providing evidence for long-term functional deficits. The present paper will review progress made to date within this field of research. collapse abstract

An IL-7 fusion protein that shows increased thymopoietic ability.

The role of IL-7 during thymopoiesis has led to it being the focus of a number of therapeutic interventions. However, its small size and pleiotropic nature present problems for thymus-directed therapies. We have created a fusion molecule between the ... expand abstractextracellular N-terminal domain of CCR9 and IL-7, which has the potential to overcome these difficulties. This novel fusion protein retains the thymopoietic activity of IL-7 and the ligand-binding ability of CCR9. As a thymopoietic agent, compared with IL-7, it shows an enhanced retention in the thymus, increased de novo T cell production, and increased thymic output. Old mice receiving the fusion protein show improved CD8 T cell responses and reduced viral load after infection with influenza virus compared with those receiving IL-7. This chimeric molecule offers a novel therapeutic strategy that may result in the production of an effective immunorestorative agent. collapse abstract

CD25-expressing CD8+ T cells are potent memory cells in old age.

We have recently described an IL-2/IL-4-producing CD8+CD25+ non-regulatory memory T cell population that occurs in a subgroup of healthy elderly persons who characteristically still have a good humoral response after vaccination. The present study ad... expand abstractdresses this specific T cell subset and investigates its origin, clonal composition, Ag specificity, and replicative history. We demonstrate that CD8+CD25+ memory T cells frequently exhibit a CD4+CD8+ double-positive phenotype. The expression of the CD8 alphabeta molecule and the occurrence of signal-joint TCR rearrangement excision circles suggest a thymic origin of these cells. They also have longer telomeres than their CD8+CD25- memory counterparts, thus indicating a shorter replicative history. CD8+CD25+ memory T cells display a polyclonal TCR repertoire and respond to IL-2 as well as to a panel of different Ags, whereas the CD8+CD25- memory T cell population has a more restricted TCR diversity, responds to fewer Ags, and does not proliferate in response to stimulation with IL-2. Molecular tracking of specific clones with clonotypic primers reveals that the same clones occur in CD8+CD25+ and CD8+CD25- memory T cell populations, demonstrating a lineage relationship between CD25+ and CD25- memory CD8+ T cells. Our results suggest that CD25-expressing memory T cells represent an early stage in the differentiation of CD8+ cells. Accumulation of these cells in elderly persons appears to be a prerequisite of intact immune responsiveness in the absence of naive T cells in old age. collapse abstract

Improved thymic function in exclusively breastfed infants is associated with higher interleukin 7 concentrations in their mothers' breast milk.

BACKGROUND: In rural Gambians, the season of birth strongly predicts adult mortality. Those born during the harvest season have longer life spans than do those born during the hungry season, and the deaths associated with infectious diseases suggest ... expand abstractpermanent early-life influences on immunity. Thymic measurements showed significantly smaller thymuses in infants born during the hungry season than in those born during the harvest season. The differences were greatest at 8 wk of age, a time when all infants were exclusively breastfed, which suggests the involvement of breast milk factors. OBJECTIVE: This study tested whether thymic size differences reflect thymic output and ascertained whether thymic output is associated with breast milk interleukin 7 (IL-7) concentrations. DESIGN: We studied thymic size and output in a prospective cohort of 138 Gambian infants born in either the hungry or the harvest season by measuring signal-joint T cell receptor-rearrangement excision circles (sjTRECs) at birth and at 8 wk of age. IL-7 concentrations in breast milk were measured by using an enzyme-linked immunosorbent assay. RESULTS: By age 8 wk, those born in the hungry season had significantly lower sjTREC counts than did those born in the harvest season (0.97 and 2.12 sjTRECs/100 T cells, respectively; P = 0.006). At 1 wk postpartum, the breast milk of mothers of infants born in the hungry season had significantly lower IL-7 than did that of mothers of infants born in the harvest season (79 and 100 pg/mL, respectively; P = 0.02). The findings were similar at 8 wk postpartum. CONCLUSION: These data show a plausible pathway linking external seasonal insults to mothers with thymic development in their infants, which suggests possible implications for long-term programming of immunity. collapse abstract

Interleukin-7: an interleukin for rejuvenating the immune system.

Infection of an individual (aged 20-30 years) by a virus will cause a response from the T (thymus derived) lymphocytes of which there are approximately 3 x 10(11). If the individual has not met the virus before, the response will come from the naive ... expand abstractT cell subset (50 +/- 10% of the total T cell pool at this age) containing recent thymic emigrants produced from the thymus at approximately 10(8) per day. Their antigen-specific receptor has a defined specificity governed by the conformation of its two chains (alpha and beta), and the repertoire of specificities is somewhere in the region of 2 x 10(7) to 10(8). A successful response leads to clonal expansion and the generation of memory T cells to the infecting agent. collapse abstract

Reversal of thymic atrophy.

Age-associated thymic atrophy is a key event preceding the inefficient functioning of the immune system, resulting in a diminished capacity to generate new T-cells. This thymic involution has been proposed to be due to changes in the thymic microenvi... expand abstractronment resulting in its failure to support thymopoiesis. A key cytokine in the early stages of thymocyte development is IL-7 and expression levels are greatly reduced with age. The ability of IL-7 to restore the immune system by enhancing thymic output remains controversial. In this review, we highlight the advances in molecular approaches used to evaluate recent thymic emigrants and assess the success of these strategies in determining whether IL-7 can lead to immune reconstitution. collapse abstract

Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection.

OBJECTIVES: We aimed to provide evidence of thymic reconstitution after highly active antiretroviral therapy (HAART) in HIV-1 infected patients and to correlate this with the restoration of peripheral naïve T cells. METHODS: Positron emission tomogra... expand abstractphy (PET) enables definitive evidence of thymic activity, indicating functional potential. In this case study, a single patient who initiated HAART demonstrated reconstitution of the naïve T-cell pool and underwent thymic PET scans at baseline and 2 and 6 months following initiation of therapy. Two patients who failed to demonstrate such reconstitution acted as controls. These patients (mean age 27 years) had chronic HIV infection with low CD4 T-cell counts (mean 82, range 9-160 cells/microL blood). Increased function of the thymus visualized by PET was correlated with phenotypic changes in CD4 and CD8 T cells in the periphery measured by flow cytometry, and with numbers of recent thymic emigrants measured by quantification of the numbers of T-cell receptor excision circles (TRECs) in peripheral cells. RESULTS: In one patient, clear correlations could be drawn between visible activity within the thymus, as measured by increased [F18]fluorodeoxyglucose (FDG) uptake, and regeneration of naïve CD4 (CD45RA/CD62L) T cells, increased numbers of CD4 T cells, controlled viraemia and increased numbers of recent thymic emigrants. A second patient displayed no increase in peripheral CD4 count and no increase in thymic activity. The third patient elected to stop therapy following the 2-month time point. CONCLUSIONS: The use of PET suggests that thymic activity may increase after HAART, indicating that the thymus has the potential to be functional even in HIV-1 infected persons with low CD4 T-cell counts. collapse abstract

Age-related changes in the function of T cells.

At the start of the last century in the United Kingdom, only 24% of the 587,830 deaths registered were of individuals over 65, but by the end of the century these figures had changed markedly. Of the 558,052 deaths in 1997, 84% were in the population... expand abstract over 65. This "right shift" in the survival curve is projected to continue. The UK Government Actuary's Department forecast that by 2020, 11.75 million people (19% of the population) will be over 65 rising to 15.1 million people (25% of the population) by 2040. Older members of society show infections of the urinary tract, respiratory tract, skin, soft tissue or intra-abdominal region, infectious endocarditis, bacterial meningitis, tuberculosis, and herpes zoster, at a higher incidence than among younger adults. Moreover, mortality rates for these diseases are often 2-3 times higher among elderly patients than younger individuals with the same disease. The higher morbidity and mortality from these infections, plus the increased prevalence of specific cancers and certain autoimmune diseases point to an immune system deteriorating with age. At the core of the immune system are the T cells and this review analyses possible causes for the changes in T cell function that may account for the deterioration of the immune system. Any intervention to reverse the decline in the immune system must have a rational basis built on a hypothesis-driven inquiry, and one such intervention process is presented here. collapse abstract

My T's gone cold, I'm wondering why.

Thymic output during initial highly active antiretroviral therapy (HAART) and during HAART supplementation with interleukin 2 andor with HIV type 1 immunogen (Remune).

The thymic output of patients receiving highly active antiretroviral therapy (HAART) was assessed by sjTREC (signal joint T cell receptor rearrangement excision circle) analysis to determine the thymic contribution to CD4(+) T cell reconstitution dur... expand abstracting initial therapy and during interleukin 2 (IL-2) and/or Remune supplementation of HAART. Levels of sjTRECs were observed to decline dramatically after the first 4 weeks of HAART and then increased without significant associated changes in CD4(+) T cell counts. HAART supplementation with IL-2 was observed to lead to rapid increases in CD4(+) T cells that were accompanied by sjTREC decreases. No notable changes in CD4(+) T cell counts and sjTRECs were seen in patients receiving HAART supplemented with Remune alone. The results indicate CD4(+) T cell maintenance during initial treatment of HIV-1 with HAART and early CD4(+) T cell reconstitution of patients receiving IL-2 with HAART is largely due to thymus-independent mechanisms, with the thymus making a limited contribution. collapse abstract

Age-associated changes in thymopoiesis.

Molecular quantitation of thymic output in mice and the effect of IL-7.

Aging of the murine thymus is accompanied by a measurable loss of weight and cellularity and a marked reduction in its output of T lymphocytes. This study employs a molecular approach to determine changes in the output of the murine thymus using a no... expand abstractvel assay system based on the detection and quantitation of the excised TCRdelta DNA locus from within the TCRalpha chain genes. In alpha beta(+) T cells such delta excision circles (deltaEC) are present at higher levels in naive T cells as compared with memory T cell populations, are non-replicating, and diluted within the total peripheral alpha beta(+) T cell pool with advancing age. This assay permits the assessment of thymic output in older animals where previous analysis was hampered by the transient nature of the naive T cell surface phenotype, and so allows the assessment of the efficacy of IL-7 as an agent to reverse thymic atrophy. Treatment of old mice with IL-7 although producing no overall change in the total number of alpha beta(+) T cells in the peripheral T cell pool altered the component subsets. Mice treated with IL-7 showed increases in the number of alpha beta(+)TCR cells possessing deltaEC commensurate with improved thymic output, and the splenic T cells from IL-7-treated mice performed significantly better in in vitro functional assays compared to those from age-matched saline-treated controls. collapse abstract

Age-associated thymic atrophy is linked to a decline in IL-7 production.

Age-associated thymic atrophy results in a decline in T lymphocyte output and has been identified as one of the key events that precede inefficient functioning of the immune system in later life. Thymic atrophy is thought to result from a failure of ... expand abstractthe thymic microenvironment to support thymopoiesis in old age and recent evidence suggests that a decline in interleukin-7 (IL-7) expression may limit thymocyte development by restricting combinations of survival, proliferation and rearrangement of the TCRbeta chain. Using RT-PCR and the RNase protection assay, we show that the expression of IL-7 declines with age. Analysis of Connexin 43 expression, a component molecule of gap junctions, whose function is to connect epithelial cells, does not markedly decline with age. These observations suggest that a decline in IL-7 expression is not matched by a similar loss of epithelial cells. These results in conjunction with other studies lead us to speculate that IL-7 producing MHC class II positive TECs are being replaced by cells that do not have this capacity. collapse abstract

Thymic activity in late-stage HIV-1 infected individuals receiving highly active antiretroviral therapy: potential effect of steroid therapy.

OBJECTIVE: Our objective was to monitor the effect of steroid therapy on the thymic output and function of late-stage HIV-1-infected patients undergoing highly active antiretroviral therapy (HAART). DESIGN: The indirect measurement of T cells that ha... expand abstractve recently emigrated from the thymus as a means of quantifying thymic output, and therefore thymic function, was achieved through use of the polymerase chain reaction-based signal joint T cell receptor rearrangement excision circles (sjTREC) assay. Proliferative capacity and interleukin (IL)-2 and IL-4 production by T cells after antigenic, mitogenic and IL-2 stimulation were also analysed. METHOD: Measurements were made of sjTREC levels in peripheral blood mononuclear cell DNA samples from five HIV-1 infected patients (one on steroid therapy prior to and at the time of sample extraction) receiving HAART. IL-2 and IL-4 production and proliferative capacity were also measured in three patients, including the patient receiving steroids. RESULT: The sjTREC assay gave an extremely weak result for the patient on steroids but, under the same assay conditions, provided clear, positive readings for the four patients not on steroids. Comparison of the patients' cytokine profiles revealed that IL-2 production was generally low or absent in all three patients tested but that IL-4 production was significantly higher in the patient given steroids. Functional potential as revealed by proliferation assays showed very low or absent cellular proliferation. CONCLUSION: The thymic contribution to the restoration of T lymphocyte numbers, particularly during the treatment of HIV-1 infection, may become compromised if thymic inhibitory factors such as steroids are used. Furthermore, the use of steroids may also favour the development of a T helper 2 response, which could prove particularly undesirable during HIV-1 infection. collapse abstract

Age-associated thymic atrophy is not associated with a deficiency in the CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) thymocyte population.

Age-associated thymic atrophy has been proposed to be due to changes in both the thymic microenvironment and in the intrinsic properties of the early T cell progenitors, the CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) cells. We have purified these cells from th... expand abstracte thymus of both old and young mice and demonstrate no age-associated defect in their ability to differentiate into their progeny in vitro when used to reconstitute fetal thymic organ cultures. We also demonstrate that in the presence of anti-IL-7, CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) cells from young mice show reduced thymocyte development in fetal thymic organ cultures compared with controls. Finally we have shown that old mice treated with IL-7 show improved thymopoiesis compared with control groups. The increased thymopoiesis seen in the old animals occurs in the sequential manner which would be anticipated for an agent working directly on the early stages, including the CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) cells. collapse abstract

Both age and gender affect thymic output: more recent thymic migrants in females than males as they age.

The thymus undergoes age-associated involution, with studies showing thymic size decreasing from birth at a rate of approximately 3% per year until middle age, and at a rate of 1% per year thereafter. The aim of this study was to determine the effect... expand abstract of thymic atrophy on T-lymphocyte production by the thymus, and to clarify the ongoing uncertainty regarding gender differences in thymic function. We quantified recent thymic emigrants (RTEs) in blood through the measurement of signal joint T-cell receptor rearrangement excision circles (sjTRECs), and showed that the decline in the number of RTEs in the blood with increasing age is gender-linked. Peripheral blood from females contained significantly higher levels of sjTRECs per CD3+ T cell than blood from males (P = 0.002), despite there being no significant gender difference in the absolute number of CD3+ T cells in the populations analysed (P > 0.10). Our findings suggest better thymic function in females compared with males, providing females with a higher number of recent thymic emigrants for longer periods of life. Such a finding provides a plausible explanation for the immunological gender differences observed in previous studies and possibly, for the general longer life expectancy in females compared with males. collapse abstract

Il-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice.

Thymic atrophy is an age-associated decline in commitment to the T cell lineage considered to be associated with defective TCR beta-chain rearrangement. Both IL-7 and stem cell factor (SCF) have dominant roles at this stage of triple negative (TN) th... expand abstractymocyte development. Because there is no age-associated decrease in the number of CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) cells, this study investigated whether alterations in apoptosis within the TN pathway accounted for diminishing thymocyte numbers with age. Here we show significant age-associated increases in apoptotic TN thymocytes, specifically within CD44(+)CD25(+) and CD44(-)CD25(+) subpopulations, known to be the location of TCR beta-chain rearrangement. IL-7 added to TN cultures established from old mice significantly both reduces apoptosis and increases the percentage of live cells within CD44(+)CD25(+) and CD44(-)CD25(+) subpopulations after 24 h, with prosurvival effects remaining after 5 days. SCF failed to demonstrate prosurvival effects in old or young cultures, and IL-7 and SCF together did not improve upon IL-7 alone. IL-7R expression did not decline with age, ruling out the possibility that the age-associated increase in apoptosis was attributed to reduced IL-7R expression. Compared with PBS, treatment of old mice with IL-7 produced significant increases in live TN cells. By comparison, treatment with SCF failed to increase live TN numbers, and IL-7 and SCF together failed to significantly improve thymopoiesis above that shown by IL-7 alone. Thus, treatment with IL-7 alone can reverse the age-associated defect in TN thymocyte development revealed by in vitro studies to be located at the stages of TCR beta-chain rearrangement. collapse abstract

Effect of CD4(+) and CD8(+) cell depletion on wound healing.

BACKGROUND: Depression of the immune system can result in poor or delayed wound healing. METHODS: Thymectomized rats were depleted of CD4(+) and CD8(+) lymphocytes by intraperitoneal injection of Medical Research Council Oxford (MRC OX)38 antibodies ... expand abstractand MRC OX8. Significant depletion was demonstrated throughout the wound healing process by immunofluorescence studies of peripheral blood. Following depletion the rats underwent laparotomy incisions which were allowed to heal for 10 weeks. Differences in healing were demonstrated by analysing the wounds biomechanically by tensiometry to obtain values of ultimate strength, resilience, toughness, maximum extension and elastic constant. RESULTS: Wounds of animals depleted of CD4+ lymphocytes showed a significant decrease in ultimate strength, resilience and toughness. Wounds of animals depleted of CD8(+) lymphocytes showed a significant increase in ultimate strength, resilience and toughness. CONCLUSION: Wounds healed in the absence of T lymphocytes. However, the subsets have an opposing regulatory role, with CD4(+) lymphocytes upregulating and CD8(+) lymphocytes downregulating wound healing. Presented to the Surgical Research Society in Nottingham, UK, 11 July 1997 and published in abstract form as Br J Surg 1997; 84: 1618 collapse abstract

Erythrocyte transfusion causes immunosuppression after total hip replacement.

A prospective study of 34 patients undergoing total hip replacement was done to determine whether homologous erythrocyte transfusion causes postoperative immunosuppression. In the transfused patient group (14 patients), there was a reduction in CD3+ ... expand abstractand CD3+4+ cell numbers at Day 2, returning to preoperative levels by Day 7. In contrast, in the untransfused patient group (20 patients), there was no significant depression in these lymphocyte subgroups at Day 2 and an increase in total lymphocyte, CD3+, CD3+4+, and CD3+4-8- cell numbers at Day 7. In both patient groups there was postoperative leukocytosis, granulocytosis, and monocytosis at Days 2 and 7, with no significant change in postoperative B (CD19+) cell numbers, natural killer cells, or the minor T cell populations of CD3+4+8+ and CD3+25+. The lymphocyte functional test of Candida recall was significantly impaired at Day 7 in the transfused patient group, where Candida recall is a memory T cell response to an antigen extracted from the yeast Candida Albicans. These findings suggest that homologous erythrocyte transfusion after hip replacement surgery causes cell mediated immune suppression. The main clinical implication of the current study is that perioperative homologous erythrocyte transfusion may place patients at greater risk of infectious complications, including infection of the prosthesis. collapse abstract