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Helios Expressing Regulatory T Cells are Correlated with Decreased IL-2 Producing CD8 T Cells and Antibody Diversity in Mozambican Individuals Living Chronically HIV-1

Article scientifique 2021 Anglais

Résumé

Abstract Background: Human immunodeficiency virus type 1 (HIV-1) causes impairment of T and B cell responses, which begins during the acute phase of infection and is not completely restored by antiretroviral treatment. Regulatory T cell (Tregs) can improve overall disease outcome by controlling chronic inflammation, but may also suppress beneficial HIV-1 specific immune responses. We analyzed immune alterations, including Tregs, and their clinical significance in Mozambican people living chronically with HIV-1 (PLWH-C). Results: In PLWH-C, the proportion of total Tregs was positively correlated with the proportion of IL-2+CD4 T cells (r=0.647; p=0.032) and IL-2+IFNg+CD8 T cells (r=0.551; p=0.014), while the Helios+Tregs correlated inversely with levels of IL-2+CD8 T cells (r= -0.541; p=0.017). Overall, PLWH-C, with (82%) or without virologic suppression (64%), were seronegative for at least HIV-1 p31, gp160 or p24, and the breadth of antibody responses was positively correlated with proportions of CD38+HLA-DR+CD8 T cells (r=0.620; p=0.012), viral load (r=0.452; p=0.040) and inversely CD4 T cells count (r=-0.481; p=0.027). Analysis of all individuals living HIV-1 showed that the breadth of HIV-1 antibody responses was inversely correlated with the proportion of Helios+Tregs (r=-0.45; p=0.02). Conclusion: Among Mozambican patients living with HIV-1, seronegativity to some HIV-1 proteins is common mostly in virologically suppressed individuals. Low diversity of HIV-specific antibodies is correlated to indicators of disease control during ART. Elevation in the proportion of Helios+Tregs is related to a reduction of CD8 T expressing intracellular IL-2 but may contribute to impairment of B cell function.

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Chissumba, R., Magul, C., Macamo, R., Monteiro, V., Enosse, M., Macicame, I., Cumbane, V., Bhatt, N., Viegas, E., Imbach, M., Eller, L., Polyak, C., Kestens, L., Jani, I. (2021). Helios Expressing Regulatory T Cells are Correlated with Decreased IL-2 Producing CD8 T Cells and Antibody Diversity in Mozambican Individuals Living Chronically HIV-1. https://doi.org/10.21203/rs.3.rs-778117/v1

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Raquel Matavele Chissumba Cacildo Magul Rosa Macamo Vânia Monteiro Maria Enosse Ivalda Macicame Victória Cumbane Nilesh Bhatt Edna Viegas Michelle Imbach Leigh Anne Eller Christina S. Polyak Luc Kestens Ilesh Jani

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