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NK cytotoxicity against CD4 + T cells during HIV-1 infection: A gp41 peptide induces the expression of an NKp44 ligand

2005; National Academy of Sciences; Volume: 102; Issue: 31 Linguagem: Inglês

10.1073/pnas.0504315102

1091-6490

Vincent Vieillard, Jack L. Strominger, Patrice Debré,

T-cell and B-cell Immunology

HIV infection leads to a state of chronic immune activation and progressive deterioration in immune function, manifested most recognizably by the progressive depletion of CD4 + T cells. A substantial percentage of natural killer (NK) cells from patients with HIV infection are activated and express the natural cytotoxicity receptor (NCR) NKp44. Here we show that a cellular ligand for NKp44 (NKp44L) is expressed during HIV-1 infection and is correlated with both the progression of CD4 + T cell depletion and the increase of viral load. CD4 + T cells expressing this ligand are highly sensitive to the NK lysis activity mediated by NKp44 + NK cells. The expression of NKp44L is induced by the linear motif NH2-SWSNKS-COOH of the HIV-1 envelope gp41 protein. This highly conserved motif appears critical to the sharp increase in NK lysis of CD4 + T cells from HIV-infected patients. These studies strongly suggest that induction of NKp44L plays a key role in the lysis of CD4 + T cells by activated NK cells in HIV infection and consequently provide a framework for considering how HIV-1 may use NK cell immune surveillance to trigger CD4 + T cells. Understanding this mechanism may help to develop future therapeutic strategies and vaccines against HIV-1 infection.