Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation

Author:

Lal Kerri,Phuang-Ngern Yuwadee,Suhkumvittaya Suchada,Leeansyah Edwin,Alrubayyi AljawharahORCID,Dias JoanaORCID,Waickman Adam,Kim Dohoon,Kroon Eugène,Pinyakorn Suteeraporn,Eller Leigh,Maciel Jr. Milton,Rerknimitr Rungsun,Chomchey Nitiya,Phanuphak Nittaya,de Souza Mark,Nitayaphan Sorachai,Ake Julie,Vasan Sandhya,Robb MerlinORCID,Ananworanich Jintanat,Sandberg JohanORCID,Schuetz Alexandra,Eller MichaelORCID,Paquin-Proulx DominicORCID

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.

Funder

U.S. Department of Defense

Swedish Research Council

Swedish Cancer Society

Center for Innovative Medicine

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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