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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 with HIV-1
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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 aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response 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+IFNγ+CD8 T cells (r = 0.551; p = 0.014), while the proportions of 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 with absolute 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 people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of Helios+Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.
Springer Science and Business Media LLC
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
Julie Ake
Khelvon De Araujo
Nilesh Bhatt
Igor Capitine
Raquel Matavele Chissumba
Alberto Machaze
Eduardo Namalamgo
Celso Castiano
Emelva Manhiça
Mirna Mutombene
Ducília Matimbe
Onélia Guiliche
Vania Mapossa
Vania Monteiro
Nilzio Cavele
Trevor Crowell
Leigh Anne Eller
Zebiba Hassen
Michelle Imbach
Luis Inhambizo
Qun Li
Ivalda Macicame
Ferrao Mandlate
Carmélia Massingue
Mark Milazzo
Vanessa Monteiro
Chiaka Nwoga
Christina S. Polyak
Patrícia Ramgi
Merlin L. Robb
Steve Schech
Gail Smith
Edith M. Swann
Edna Viegas
Adam Yates
Title: Helios expressing regulatory T cells are correlated with decreased IL-2 producing CD8 T cells and antibody diversity in Mozambican individuals living chronically with HIV-1
Description:
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 aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response 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+IFNγ+CD8 T cells (r = 0.
551; p = 0.
014), while the proportions of 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 with absolute 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 people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals.
Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C.
Elevation in the proportion of Helios+Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.
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