RTR with TLR4 polymorphism present a lower risk of post-transplant atherosclerotic events and acute allograft rejection, but experience severe infectious episodes more frequently. This subset of RTR may benefit from a less potent immunosuppression regimen, along with increased preventive measures against infectious agents.

HLA‐G displays immunotolerogenic properties towards the main effector cells involved in graft rejection through inhibition of NK‐ and CTL‐mediated cytolysis and CD4+ T cell alloproliferation. HLA‐G expression is restricted in healthy tissues to trophoblast and thymus but is extended to various tissues under pathological conditions. HLA‐G was detected in allograft biopsies and sera from transplanted patients who displayed a better graft acceptance. However, the cells involved in such de novo expression of HLA‐G remain to be characterized. By flow cytometry and confocal microscopy, we demonstrated that, following allogeneic stimulation in vitro, both CD4+ and CD8+ T cell subsets can express membrane‐bound HLA‐G1 and/or soluble HLA‐G5molecules. Such HLA‐G1/‐G5 expression is regulated at the transcriptional level. Soluble HLA‐G5 could be detected by using a novel monoclonal antibody, 5A6G7, specific for the intron 4‐retaining sequence of HLA‐G5. Finally, the biological relevance of these data was provided by analysis of transplanted patients in whom we identified both CD4+ and CD8+ T cells expressing HLA‐G. The HLA‐G‐positive T cells we describe here may constitute a cellular source of HLA‐G after allotransplantation and may be involved in the improved graft acceptance which is observed in HLA‐G‐positive transplanted patients.

Prolonged CD4 T cell lymphopenia after administration of polyclonal anti-thymocyte globulins increases the rate of posttransplantation morbidity, but whether impaired immune reconstitution affects survival is unknown. We studied the effect of CD4 T cell lymphopenia on survival in 302 consecutive prevalent renal transplant recipients and the role of thymic function in CD4 T cell reconstitution and posttransplantation outcomes in 100 consecutive incident renal transplant recipients. We followed the prevalent cohort for a mean duration of 92 months. Of these 302 patients, 81 (27%) had persistent CD4 T cell counts Ͻ300/mm 3 and 36 (12%) died during follow-up. We observed a higher death rate in patients with CD4 T cell lymphopenia persisting for Ͼ1 year (24.1 versus 7.6%; P Ͻ 0.001). Furthermore, in Cox regression analysis, CD4 T cell lymphopenia associated with a nearly five-fold risk for death (adjusted hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.91 to 10.65; P ϭ 0.001). In the incident cohort, we estimated thymic function by T cell receptor excision circles (TRECs) per 150,000 CD3 ϩ cells, which predicted efficient CD4 T cell reconstitution. Higher pretransplantation TREC values associated with lower risks for cancer (adjusted HR 0.39; 95% CI 0.15 to 0.97; P ϭ 0.046) and infection (HR 0.29; 95% CI 0.11 to 0.78; P ϭ 0.013). In summary, prolonged polyclonal anti-thymocyte globulin-induced CD4 T cell lymphopenia is an independent risk factor for death. Determination of pretransplantation thymic function may identify patients at higher risk for CD4 T cell lymphopenia and posttransplantation morbidity, including cancer and infections. Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. These polyclonal antibodies are a complex mixture of antibodies with multiple specificities directed to both T and non-T cells. 1,2 These antibodies produce profound T cell depletion via complement-dependent lysis and Fas/Fas ligand-mediated apoptosis. 3,4 Although T cell regeneration generally occurs in the months after ATG administration, Muller et al. 5 reported that ATG may induce persistent changes in T cell subsets characterized by a low CD4 T cell count and a CD8 T cell expansion.