NKG2C is a major triggering receptor involved in the V[delta]1 T cell-mediated cytotoxicity against HIV-infected CD4 T cells.
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.
Fausther-Bovendo
Hugues
H
Institut National de la Santé et de la Recherche Scientifique U543, Université Pierre et Marie Curie Paris-6, France.
Wauquier
Nadia
N
Cherfils-Vicini
Julien
J
Cremer
Isabelle
I
Debré
Patrice
P
Vieillard
Vincent
V
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006680:HLA Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation; D055654:NK Cell Lectin-Like Receptor Subfamily C; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D019562:Viral Load; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human