Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1

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-g are potent inducers of Ly6C and Sca-1 in naive mouse CD4(+) and CD8(+) T cells, whereas TGF-beta limits their expression. The induction of Ly6C and Sca-1 by IL-27 and IFN-g 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 Toxoplasma gondii, pathogen-specific T cells expressed high levels of these molecules and in this context, endogenous IL-27 and IFN-g 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.