Age-dependent immune response after organ transplantation

Abstract

Recipients older than 65 years represent the fastest growing patient group on the waiting list for organ transplantation. However, little is known about the consequences of the aging immune response on transplant outcome. Moreover an age dependent immune response may have important implications for an age adapted immunosuppression after transplantation. Thus, we investigated the age-dependent effector and regulatory T-cell response in an experimental murine transplant model.Phenotype and function of effector/memory T-cells and regulatory T-cell function were analyzed in young (3 mths) and old (18 mths) naive B6 mice and in Wild type (WT) skin transplant recipients.First proliferation, cytokine secretion and CD4+ T-cell phenotypes were analyzed in naive mice. While a higher percentage of effector/memory T-cells (CD4+CD44highCD62Llow, p<0.005) was found in old naive B6 mice, in vitro proliferation and IFNγ-production were significantly reduced (ELISPOT; MLR p<0.001).Likewise old WT skin graft recipients demonstrated a modified immune response. A significantly prolonged graft survival was associated with an impaired in vitro proliferation (MLR: p<0.01) und IFNγ-production (ELISPOT; p<0.001). CD4+ T-cells expressing early activation markers (CD69+), cytokine (IFNγ+, IL-2+ and chemokine receptors (CXCR3+, CCR5+) were significantly elevated in old recipients. As our results demonstrate an altered effector T-cell response with increasing age, we further sought to examine regulatory mechanisms in old recipients. Interestingly, old regulatory T-cells (CD4+CD25+FoxP3+) showed a well preserved suppressive function which was comparable to young regulatory T-cells.In summary a reduced migratory and proliferative capacity of old effector T-cells and a well preserved regulatory T-cell function was observed. Therefore the balance between effector and regulatory mechanisms may be altered with increasing recipient age contributing to prolonged graft survival. These observations may have important clinical implications in regard to an age adapted immunosuppressive regimen.