The gp49B1 inhibitory receptor regulates the IFN-γ responses of T cells and NK cells

Xiaogang Gu, Amale Laouar, Junmei Wan, Massoud Daheshia, Judy Lieberman, Wayne M. Yokoyama, Howard R. Katz, N Manjunath N

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28 Scopus citations

Abstract

The magnitude and diversity of Ag-specific T cell effector activity have been proposed to be controlled by an integration of positive signals transduced by the TCR and negative signals originating from inhibitory cell surface molecules. Although the lectin family of NK cell-associated inhibitory receptors has been reported to regulate the function of murine CTLs, gp49B1, the Ig superfamily member is not known to be expressed on T cells. Moreover, the consequences of the lack of an endogenously expressed NK cell-associated inhibitory receptor on T cell functions are not known. We report that gp49B1 is expressed by nearly all activated CD8 and CD4 T cells in addition to NK cells during an immune response to viral, bacterial, or tumor challenge. Kinetics of gp49B1 expression parallel functional capability and subside in the memory phase. Following vaccinia viral infection, IFN-γ production by both subsets of T cells and NK cells is enhanced in gp49B1-deficient mice compared with gp49B1+/+ mice. The stimulation threshold for IFN-γ production is also lower in gp49B1-deficient T cells. In contrast, no significant differences were observed in the cytotoxic responses. We conclude that gp49B1 is a unique inhibitory receptor that is induced in multiple lineages of innate and adaptive immune cells during an infection and controls their IFN-γ, but not cytotoxic responses.

Original languageEnglish
Pages (from-to)4095-4101
Number of pages7
JournalJournal of Immunology
Volume170
Issue number8
StatePublished - Apr 15 2003

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    Gu, X., Laouar, A., Wan, J., Daheshia, M., Lieberman, J., Yokoyama, W. M., Katz, H. R., & Manjunath N, N. (2003). The gp49B1 inhibitory receptor regulates the IFN-γ responses of T cells and NK cells. Journal of Immunology, 170(8), 4095-4101.