Presence or absence of TGF-beta determines IL-4-induced generation of type1 or type 2 CD8 T cell subsets

CD8(+) T cells often differentiate into highly cytotoxic cells, secreting a Th1-like or type; 1 cytokine-pattern characterized by the production of IF N-gamma, However, cytotoxic, and in some reports, noncytotoxic, type 2 cell s that secrete IL-4, IL-5,or IL-10 instead of IFN-gamma, can be generated w hen CD8(+) T cells are primed in the presence of IL-4. Here, we show that I L-4 can also generate typical CD8 type 1 responses. Indeed, while presence of TGP-beta biases the development of CD8 T cells that, then, produce littl e cytolytic activity and IFN-gamma, addition of IL-4 results in the recover y of cytotoxicity and IFN-gamma production. The cooperative effects of TGF- beta and IL-4 imply dual functions, not only for IL-4, but also for TGF-bet a. Indeed, depending on the presence or absence of IL-4, TGF-beta either in hibits or induces the generation of type 1 CD8(+) T cells. Physiologically, the ratio of local IL-4/TGF-beta concentration may therefore be a critical element in determining the outcome of T cell responses to pathogen and aut oantigens. It allows CD8 T cells to switch from an immunotolerant state in the presence of only TGF-beta or IL-4, to an immunocompetent proinflammator y type 1 state in the absence or presence of both cytokines.