Ly6C expression on T cells is modulated by IL-27, interferon-gamma and TCR stimulation

Ly6C is a GPI-anchored glycoprotein expressed on a range of hematopoietic cell lineages. On T cells, its expression distinguishes short-lived effector CD4+ T cells from memory precursor effector cells. The function of Ly6C is unclear but this surface molecule is associated with homing to lymph nodes and crosslinking Ly6C with antibodies reduces T cell production of IL-2. We are investigating the factors that regulate the expression of Ly6C and their possible roles in infection. Using sorted Ly6C-negative naive T cells we found that TCR stimulation is not sufficient to induce Ly6C expression, whereas the cytokines IL-27 and interferon-gamma (IFNg) alone can induce Ly6C expression. However, this cytokine-mediated induction is enhanced by TCR stimulation. The in vivo significance of this pathway is seen during toxoplasmosis, when both naive and activated parasite specific effector CD4+ and CD8+ T cells upregulated Ly6C expression. This upregulation was reduced in mice that lack IL-27. While these results suggest that cytokines have a major role in the regulation of Ly6C expression, it remains unclear how this affects T cell function and what role cytokine-mediated expression plays in the specific expression of Ly6C on effector but not memory populations.