T细胞稳态增殖与自身免疫

T cell homeostatic proliferation associated with autoimmunity and antitumor immunity

近年有关外周T细胞群体存活与稳态的深入研究发现 :抗原活化前T细胞的存活需要自身肽 MHC复合物的作用以提供适度的存活信号 ;在淋巴细胞急剧减少的状态下 ,T细胞一样通过与自身肽 MHC复合物的作用发生稳态增殖以恢复T细胞群体的正常规模 ,这种增殖后的T细胞具显著的自身反应性且兼具效应与记忆T细胞的功能。稳态增殖后的T细胞可能参与自身免疫疾病的发生 ;与此同时 ,稳态增殖的这种特性也可用来激发特异的抗肿瘤免疫 。

Through positive and negative selection, the thymocytes with high avidity for self peptide-MHC complex were eliminated, but retained low but significant reactivity for self-peptides. After maturing and leaving the thymus, these cells continue to depend on the interaction of the TCR with self peptide-MHC complex for survival signals. Maturing T cells were regulated by homeostatic proliferation for the total size of the T cell pool at a constant level, especially at the final stage of an immune response and lymphopenia status. Homeostatic proliferation requires interaction between TCR and self peptide-MHC complex with lower avidity. Homeostatic proliferated T cells show both effecter and memory characteristics against autoantigens, and are sufficient to induce autoimmune disease. On the other hand, these characteristics also could be explored for the immunotherapy targeted nonmutated tumor associated self-antigens.