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*
Laboratoire d’Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Canada;
Department of Immunology and Oncology Centro Nacional de Biotecnologia-CSIC Universidad Autonoma Campus de Cantoblanco, Madrid Spain;
Department of Biochemistry, St. Jude Children’s Research Hospital, Memphis, TN 38101; and
§
Department of Research, Novartis Pharma, Basel, Switzerland
CD8+ T cells often differentiate into highly cytotoxic
cells, secreting a Th1-like or type 1 cytokine pattern characterized by
the production of IFN-
. However, cytotoxic, and in some reports,
noncytotoxic, type 2 cells that secrete IL-4, IL-5, or IL-10 instead of
IFN-, can be generated when CD8+ T cells are primed in
the presence of IL-4. Here, we show that IL-4 can also generate typical
CD8 type 1 responses. Indeed, while presence of TGF-ß biases the
development of CD8 T cells that, then, produce little cytolytic
activity and IFN-, addition of IL-4 results in the recovery of
cytotoxicity and IFN- production. The cooperative effects of TGF-ß
and IL-4 imply dual functions, not only for IL-4, but also for TGF-ß.
Indeed, depending on the presence or absence of IL-4, TGF-ß either
inhibits or induces the generation of type 1 CD8+ T cells.
Physiologically, the ratio of local IL-4/TGF-ß concentration may
therefore be a critical element in determining the outcome of T cell
responses to pathogen and autoantigens. It allows CD8 T cells to switch
from an immunotolerant state in the presence of only TGF-ß or IL-4,
to an immunocompetent proinflammatory type 1 state in the absence or
presence of both cytokines.
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