A Self-Reactive TCR Drives the Development of Foxp3(+) Regulatory T Cells That Prevent Autoimmune Disease

作者：Killebrew Justin R; Perdue Nikole; Kwan Alan; Thornton Angela M; Shevach Ethan M; Campbell Daniel J^*

来源：The Journal of Immunology, 2011, 187(2): 861-869.

DOI：10.4049/jimmunol.1004009

Although Foxp3(+) regulatory T cells (Tregs) are thought to express autoreactive TCRs, it is not clear how individual TCRs influence Treg development, phenotype, and function in vivo. We have generated TCR transgenic mice (termed SFZ70 mice) using Tcra and Tcrb genes cloned from an autoreactive CD4(+) T cell isolated from a Treg-deficient scurfy mouse. The SFZ70 TCR recognizes a cutaneous autoantigen and drives development of both conventional CD4(+) Foxp3(-) T cells (T-conv) and Foxp3(+) Tregs. SFZ70 Tregs display an activated phenotype evidenced by robust proliferation and expression of skin-homing molecules such as CD103 and P-selectin ligand. Analysis of Foxp3-deficient SFZ70 mice demonstrates that Tregs inhibit T-conv cell expression of tissue-homing receptors and their production of proinflammatory cytokines. In addition, Treg suppression of SFZ70 T-conv cells can be overcome by nonspecific activation of APCs. These results provide new insights into the differentiation and function of tissue-specific Tregs in vivo and provide a tractable system for analyzing the molecular requirements of Treg-mediated tolerance toward a cutaneous autoantigen. The Journal of Immunology, 2011, 187: 861-869.

• 出版日期2011-7-15