Interferon γ Derived from CD4+ T Cells Is Sufficient to Mediate T Helper Cell Type 1 Development |
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Authors: | Adil E Wakil Zhi-En Wang James C Ryan Deborah J Fowell Richard M Locksley |
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Institution: | From the *Department of Medicine and the Department of Microbiology/Immunology, and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; and the §Veterans Administration Medical Center, San Francisco, California 94121 |
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Abstract: | Interferon γ (IFN-γ) has been implicated in T helper type 1 (Th1) cell development through its ability to optimize interleukin 12 (IL-12) production from macrophages and IL-12 receptor expression on activated T cells. Various systems have suggested a role for IFN-γ derived from the innate immune system, particularly natural killer (NK) cells, in mediating Th1 differentiation in vivo. We tested this requirement by reconstituting T cell and IFN-γ doubly deficient mice with wild-type CD4+ T cells and challenging the mice with pathogens that elicited either minimal or robust IL-12 in vivo (Leishmania major or Listeria monocytogenes, respectively). Th1 cells developed under both conditions, and this was unaffected by the presence or absence of IFN-γ in non-T cells. Reconstitution with IFN-γ–deficient CD4+ T cells could not reestablish control over L. major, even in the presence of IFN-γ from the NK compartment. These data demonstrate that activated T cells can maintain responsiveness to IL-12 through elaboration of endogenous IFN-γ without requirement for an exogenous source of this cytokine. |
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Keywords: | T helper type 1 cells interferon γ natural killer cells Leishmania Listeria |
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