1. Longitudinal Analysis of Peripheral and Colonic CD161 + CD4 + T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation.
- Author
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Lal KG, Phuang-Ngern Y, Suhkumvittaya S, Leeansyah E, Alrubayyi A, Dias J, Waickman A, Kim D, Kroon E, Pinyakorn S, Eller LA, Maciel M Jr, Rerknimitr R, Chomchey N, Phanuphak N, de Souza MSS, Nitayaphan S, Ake JA, Vasan S, Robb ML, Ananworanich J, Sandberg JK, Schuetz A, Eller MA, and Paquin-Proulx D
- Subjects
- Adult, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, Biomarkers, Biopsy, CD4-Positive T-Lymphocytes metabolism, Cytokines metabolism, Female, HIV Infections drug therapy, HIV Infections metabolism, Humans, Immunophenotyping, Lymphocyte Activation, Male, Middle Aged, NK Cell Lectin-Like Receptor Subfamily B metabolism, Receptors, Antigen, T-Cell metabolism, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Young Adult, CD4-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV Infections virology, HIV-1 physiology
- Abstract
CD161 expression on CD4
+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART.- Published
- 2020
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