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*
Institut National de la Santé et de la Recherche Médicale (INSERM), U25, and Centre de l’Association Claude Bernard, Hôpital Necker, Paris, France; and
Howard Hughes Medical Institut, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
NK T cells are an unusual subset of T lymphocytes. They express
NK1.1 Ag, are CD1 restricted, and highly skewed toward Vß8 for their
TCR usage. They express the unique potential to produce large amounts
of IL-4 and IFN-
immediately upon TCR cross-linking. We previously
showed in the thymus that the NK T subset requires IL-7 for its
functional maturation. In this study, we analyzed whether IL-7 was
capable of regulating the production of IL-4 and IFN- by the
discrete NK T subset of CD4+ cells in the periphery. Two
hours after injection of IL-7 into mice, or after a 4-h exposure to
IL-7 in vitro, IL-4 production by CD4+ cells in response to
anti-TCR-
ß is markedly increased. In contrast, IFN-
production remains essentially unchanged. In
ß2-microglobulin- and CD1-deficient mice, which lack NK T
cells, IL-7 treatment does not reestablish normal levels of IL-4 by
CD4+ T cells. Moreover, we observe that in wild-type mice,
the memory phenotype (CD62L-CD44+)
CD4+ T cells responsible for IL-4 production are not only
NK1.1+ cells, but also NK1.1- cells. This
NK1.1-IL-4-producing subset shares three important
characteristics with NK T cells: 1) Vß8 skewing; 2) CD1 restriction
as demonstrated by their absence in CD1-deficient mice and relative
overexpression in MHC II null mice; 3) sensitivity to IL-7 in terms of
IL-4 production. In conclusion, the present study provides evidence
that CD4+MHC class I-like-dependent T cell populations
include not only NK1.1+ cells, but also NK1.1-
cells, and that these two subsets are biased toward IL-4 production by
IL-7.
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