Differential Role of Naive and Memory CD4+T-Cell Subsets in Primary Alloresponses

作者：Golshayan D^*; Wyss J C; Buckland M; Hernandez Fuentes M; Lechler R I

来源：American Journal of Transplantation, 2010, 10(8): 1749-1759.

DOI：10.1111/j.1600-6143.2010.03180.x

• Allorecognition
• indirect pathway
• memory T cells
• naive T cells
• transplantation

The T cell response to major histocompatibility complex (MHC) alloantigens occurs via two main pathways. The direct pathway involves the recognition of intact allogeneic MHC:peptide complexes on donor cells and provokes uniquely high frequencies of responsive T cells. The indirect response results from alloantigens being processed like any other protein antigen and presented as peptide by autologous antigen-presenting cells. The frequencies of T cells with indirect allospecificity are orders of magnitude lower and comparable to other peptide-specific responses. In this study, we explored the contributions of naive and memory CD4+ T cells to these two pathways. Using an adoptive transfer and skin transplantation model we found that naive and memory CD4+ T cells, both naturally occurring and induced by sensitization with multiple third-party alloantigens, contributed equally to graft rejection when only the direct pathway was operative. In contrast, the indirect response was predominantly mediated by the naive subset. Elimination of regulatory CD4+CD25+ T cells enabled memory cells to reject grafts through the indirect pathway, but at a much slower tempo than for naive cells. These findings have implications for better targeting of immunosuppression to inhibit immediate and later forms of alloimmunity.

• 出版日期2010-8