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.
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-infectedpatients 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.
Authors: Rachel Thomas; Hui Zhi Low; Katja Kniesch; Roland Jacobs; Reinhold E Schmidt; Torsten Witte Journal: AIDS Res Hum Retroviruses Date: 2012-05-03 Impact factor: 2.205
Authors: Carolina Garrido; Matthew L Clohosey; Chloe P Whitworth; Michael Hudgens; David M Margolis; Natalia Soriano-Sarabia Journal: JCI Insight Date: 2018-06-21
Authors: Caroline Petitdemange; Pierre Becquart; Nadia Wauquier; Vivien Béziat; Patrice Debré; Eric M Leroy; Vincent Vieillard Journal: PLoS Pathog Date: 2011-09-22 Impact factor: 6.823