MHC CLASS I-SELECTED CD4(-)CD8(-)TCR-ALPHA-BETA(+) T-CELLS ARE A POTENTIAL SOURCE OF IL-4 DURING PRIMARY IMMUNE-RESPONSE

Differentiation of naive CD4(+) lymphocytes into either Th1 or Th2 cells is influenced by the cytokine present during initial Ag priming. IL-4 is the critical element in the induction of Th2 response; however, its origin during a primary immune response is not well defined. In the present study, we characterized a novel potential source of IL-4, the class I-selected CD4(-)CD8(-)TCR-alpha beta(+) T cells. In a first set of experiments, we demonstrated that CD4(-)CD8(-)TCR-alpha beta(+) thymocytes produce a large amount of IL-4 after in vitro anti-CD3 stimulation. This phenomenon was not observed in class I-deficient mice, demonstrating that among these cells, the class I-selected subset was predominantly responsible for IL-4 production. Further studies focused on the in vivo IL-4-producing capacity of peripheral CD4(-)CD8(-)TCR-alpha beta(+) T cells. To this end, a single injection of anti-CD3 mAb, which promptly induces IL-4 mRNA expression, was used. Peripheral CD4(-)CD8(-)TCR-alpha beta(+) T cells express high levels of IL-4 mRNA in response to in vivo anti-CD3 challenge. Furthermore, analysis performed in mice lacking MHC class I or class II molecules demonstrates that both the class I-selected subset of CD4(-)CD8(-)TCR(+) and CD4(+) peripheral T lymphocytes are the major IL-4 producers after in vivo anti-CD3 stimulation. These findings suggest that class I-selected CD4(-)CD8(-)TCR-alpha beta(+) and CD4(+) T cell populations are important sources of IL-4 probably implicated in the development of specific Th2 immune responses.