Markiewicz Mary A, Wise Erica L, Buchwald Zachary S, Cheney Elizabeth E, Hansen Ted H, Suri Anish, Cemerski Saso, Allen Paul M, Shaw Andrey S
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 2009 Feb 1;182(3):1351-61. doi: 10.4049/jimmunol.182.3.1351.
Immunological synapse formation between T cells and target cells can affect the functional outcome of TCR ligation by a given MHC-peptide complex. Although synapse formation is usually induced by TCR signaling, it is not clear whether other factors can affect the efficiency of synapse formation. Here, we tested whether cytokines could influence synapse formation between murine CTLs and target cells. We found that IL-12 enhanced synapse formation, whereas TGFbeta decreased synapse formation. The enhanced synapse formation induced by IL-12 appeared to be functional, given that IL-12-treated cells could respond to weak peptides, including self-peptides, to which the T cells were normally unresponsive. These responses correlated with expression of functionally higher avidity LFA-1 on IL-12-treated CTLs. These findings have implications for the function of IL-12 in T cell-mediated autoimmunity.
T细胞与靶细胞之间免疫突触的形成会影响特定MHC-肽复合物对TCR连接的功能结果。虽然突触形成通常由TCR信号诱导，但尚不清楚其他因素是否会影响突触形成的效率。在此，我们测试了细胞因子是否会影响小鼠CTL与靶细胞之间的突触形成。我们发现IL-12增强了突触形成，而TGFβ则降低了突触形成。鉴于IL-12处理的细胞能够对包括自身肽在内的弱肽作出反应，而T细胞通常对这些弱肽无反应，因此IL-12诱导的突触形成增强似乎具有功能。这些反应与IL-12处理的CTL上功能亲和力更高的LFA-1的表达相关。这些发现对IL-12在T细胞介导的自身免疫中的功能具有启示意义。
