Lck regulates IL-10 expression in memory-like Th1 cells.

The Src family kinase Lck is thought to facilitate Th2 differentiation; however, its role in Th1 cells has not been well explored. Using mice that lack Lck in mature T cells, we find that lck(-/-) Th1 skewed cells have normal expression of T-bet and produce IFN-γ at WT levels. However, there is a 3-fold increase in IL-10 producing cells in the mutant cultures. These cells do not have elevated levels of IL-4, GATA3, IL-17 or Foxp3, indicating that they are not Th2, Th17, or Foxp3(+) T regulatory cells (Treg). Nor do these cells behave in a similar manner as the type 1 Treg. Most of the IL-10 in the lck(-/-) Th1 cultures is derived from the memory/activated subset, as the cytokine profile from Th1 cultures established from purified CD62L(+) (naïve) cells are similar to WT cells. Furthermore, this IL-10 expression appears to be dependent on IL-12 and correlates with elevated c-Maf. These data highlight a previously unappreciated role for Lck in regulating IL-10 in Th1 cells.