Functional Analysis of Alloreactive Memory CD4+ T Cells Derived from Skin Transplantation Recipient and Naïve CD4+ T Cells Derived from Untreated Mice

BackgroundMemory T cells (TMs) exhibit differential susceptibility to many immunomodulatory strategies that induce immunologic tolerance in naïve T cells, which are believed to be an important barrier to inhibiting rejection and inducing tolerance. As skin grafts are a common model for acquiring TMs, we evaluated function of TMs derived from skin grafts. We also assessed the modulatory effects on memory T cells function of the microRNAs miR-155 and miR-181a, which are involved in regulating cytokine secretion and TCR sensitivity to antigen, respectively.MethodsMemory CD4+ T cells derived from skin-graft recipient mice, and naïve CD4+ T cells from untreated mice, were isolated by negative magnetic selection, and then stimulated with dendritic cells pulsed with donor-specific antigens. Effector function and regulating mechanisms were assessed.ResultsIn contrast to naïve CD4+ T cells, CD4+ TMs stimulated with donor-specific antigen could quickly generate effector function in terms of proliferation and cytokine secretion; miR-155 and miR-181a levels in CD4+ TMs rapidly increased during immune response compared to naïve CD4+ T cells.ConclusionMemory CD4+ T cells derived from skin grafts could be used as an experimental tool for evaluating effects of different immune-modulating strategies on TMs. Levels of miR-155 and miR-181a up-regulated quickly in TMs, which could be an important mechanism by which TMs mediate immune responses rapidly.