The Potential Role of T-Cell Memory Distribution as Predisposing Factor for Rejection in Heart Transplant Recipients

Abstract

CD4 T cells play a significant role in the pathogenesis of rejection, providing help to alloreactive CD8 and B cells, however, the exact contribution of each memory compartment in vivo has not been defined. They are also important for the maintenance of tolerance due to regulatory activity of specialized subsets. In this study, we assessed changes in frequencies of functionally distinct lymphocyte subsets of peripheral blood (PBLs) in 26 heart transplant recipients (HT) in association with rejection episodes. Patients who developed rejection (n = 7), namely Grade 3B (n = 1), 3A (n = 4), or 2 (n = 2), in comparison with those with stable graft function displayed at baseline (pre-HT) higher percentages of naive (CCR7+CD45RA+) CD4 T cells (median 48 vs 36.6%; P = .035) and lower percentages of central memory (CCR7+CD45RA-) CD4 T cells (33.3 vs 46.5%; P = .035). At 30 days post-HT, CD4/CD127(low)FoxP3+ T cells were significantly reduced among patients with rejection episodes (0.84 vs 2.15%; P = .042). CD8 final effector T cells were increased at 90 days post-HT among those patients who experienced rejection (TEM2: 60.8 vs 31.9%; P < .1), at the expense of shrinking CD8 central memory compartment (TCM: 8.6 vs 12.9%; P = .046). The potential role of T-cell memory distribution should be further evaluated in HT patients as possible markers to discriminate patients at risk for rejection.