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Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers

Article scientifique 2019 Anglais

Résumé

Cytotoxic CD4+ T cells play a prominent role in chronic viral infection. CD4+ CTL clones specific for HIV-1 Nef and Gag are capable of killing HIV-1 infected CD4+ T cells and macrophages. Additionally, HIV-specific cytolytic CD4+ T cell responses in acute HIV infection are predictive of disease progression. CD57 expression on CD4s identifies cytotoxic cells. These cells are dramatically increased in chronic HIV infection. CD57 expression correlates with cytolytic granules, granzyme B and perforin expression. They express lower CCR5 compared to CD57- cells, have less HIV total DNA, and are a minor component of the HIV reservoir. CD57+ CD4+ CTLs from EC are HIV-specific, can upregulate IFNγ with Gag peptide stimulation and maintain TbethighEomes+ transcription factor phenotype. This was not observed in viraemic controllers. The maintenance of HIV-specific CD4 cytotoxic function in Elite controllers together with CD8 CTL may be important for the control of HIV viraemia and of potential relevance to cure strategies.

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Phetsouphanh, C., Aldridge, D., Marchi, E., Munier, C., Meyerowitz, J., Murray, L., Vuuren, C., Goedhals, D., Fidler, S., Kelleher, A., Klenerman, P., Frater, J. (2019). Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers. https://doi.org/10.3389/fimmu.2019.01844

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Auteur(s)

Chansavath Phetsouphanh Daniel L. Aldridge Emanuele Marchi C. Mee Ling Munier Jodi Meyerowitz Lyle Murray Cloete van Vuuren Dominique Goedhals Sarah Fidler Anthony D. Kelleher Paul Klenerman John Frater

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