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  • Title: NKG2C is a major triggering receptor involved in the V[delta]1 T cell-mediated cytotoxicity against HIV-infected CD4 T cells.
    Author: Fausther-Bovendo H, Wauquier N, Cherfils-Vicini J, Cremer I, Debré P, Vieillard V.
    Journal: AIDS; 2008 Jan 11; 22(2):217-26. PubMed ID: 18097224.
    Abstract:
    BACKGROUND: Gammadelta T cells share with natural killer (NK) cells many effector capabilities and cell-surface proteins, including the NKG2 receptor family. A subset of gammadelta T cells that express the variable Vdelta1 region plays a critical role in immune regulation, tumour surveillance and viral infection. Dramatic expansion of Vdelta1 T cells has been observed in HIV disease. OBJECTIVE: To determine if NKG2C expression on Vdelta1 T cells during HIV-1 infection is correlated with CD4 cell count and involved in lysis of CD4 T cells. METHODS: gammadelta T cells from viraemic HIV-infected patients were examined. Expression of NK cell markers was analyzed by flow cytometry. The cytolytic activity of Vdelta1 T cells was determined by either Cr-release assays or degranulation assays against HLA-E-transfected 721.221 cells or HIV-infected CD4 primary T cells. RESULTS: The expression of C-type lectin NKG2 receptors was sharply modulated on gammadelta T cells in patients with HIV infection. A profound decrease of Vdelta1 T cells bearing inhibitory NKG2A receptors corresponded to a drastic expansion of a distinct population of Vdelta1 T cells expressing a functional activating NKG2C receptor. Engagement of HLA-E, the ligand of both NKG2A and NKG2C, which is specifically induced on HIV-infected CD4 T cells, substantially enhanced the Vdelta1 T cell-mediated cytotoxicity. CONCLUSIONS: These results raise the possibility that induction of NKG2C expression on Vdelta1 T cells plays a key role in the destruction of HIV-infected CD4 T cells during HIV disease.
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