Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Immunology Discovery Research, Janssen Research and Development, LLC, Spring House, PA 19002.
J Immunol. 2018 Mar 1;200(5):1761-1770. doi: 10.4049/jimmunol.1701154. Epub 2018 Jan 22.
Ly6C and Sca-1 (Ly6A/E) are Ly6 family GPI-anchored surface molecules that are differentially expressed by multiple immune populations. Ly6C expression has been used to distinguish short-lived effector CD4 T cells from memory precursor effector cells, whereas Sca-1 has been used in the identification of CD8 memory stem cells. This study examines the expression patterns of these molecules and establishes that, in vitro, IL-27, type I IFN, and IFN-γ are potent inducers of Ly6C and Sca-1 in naive mouse CD4 and CD8 T cells, whereas TGF-β limits their expression. The induction of Ly6C and Sca-1 by IL-27 and IFN-γ is dependent on STAT1, but not STAT3 or T-bet. In mouse splenocytes, at homeostasis, Ly6C and Sca-1 expression was not restricted to effector cells, but was also found at various levels on naive and memory populations. However, in response to infection with , pathogen-specific T cells expressed high levels of these molecules and in this context, endogenous IL-27 and IFN-γ were required for the expression of Ly6C but not Sca-1. Together, these findings highlight the TCR-dependent and cytokine-mediated signals that modulate T cell expression of Ly6C and Sca-1 in vitro and in vivo during infection.
Ly6C 和 Sca-1（Ly6A/E）是 Ly6 家族的 GPI 锚定表面分子，它们在多种免疫群体中表达不同。Ly6C 的表达被用来区分短期效应 CD4 T 细胞和记忆前体效应细胞，而 Sca-1 则被用于鉴定 CD8 记忆干细胞。本研究检查了这些分子的表达模式，并确定在体外，IL-27、I 型 IFN 和 IFN-γ 是诱导幼稚 CD4 和 CD8 T 细胞中 Ly6C 和 Sca-1 表达的有效诱导剂，而 TGF-β 限制了它们的表达。IL-27 和 IFN-γ 诱导 Ly6C 和 Sca-1 的表达依赖于 STAT1，但不依赖于 STAT3 或 T-bet。在小鼠脾细胞中，在静息状态下，Ly6C 和 Sca-1 的表达不仅局限于效应细胞，而且在幼稚和记忆群体中也存在不同水平的表达。然而，在感染 后，病原体特异性 T 细胞表达高水平的这些分子，在这种情况下，内源性 IL-27 和 IFN-γ 是表达 Ly6C 所必需的，但不是 Sca-1。综上所述，这些发现强调了 TCR 依赖性和细胞因子介导的信号在感染过程中调节 T 细胞体外和体内 Ly6C 和 Sca-1 的表达。
