Functional analysis of alloreactive memory CD4 + T cells derived from skin transplantation recipient and Naïve CD4 + T cells derived from untreated mice

Background: Memory T cells (T Ms) 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 T Ms, we evaluated function of T Ms 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. Methods: Memory 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. Results: In contrast to naïve CD4 + T cells, CD4 + T Ms 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 + T Ms rapidly increased during immune response compared to naïve CD4 + T cells. Conclusion: Memory CD4 + T cells derived from skin grafts could be used as an experimental tool for evaluating effects of different immune-modulating strategies on T Ms. Levels of miR-155 and miR-181a up-regulated quickly in T Ms, which could be an important mechanism by which T Ms mediate immune responses rapidly. © 2012 Elsevier Inc. All rights reserved.