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- Title
Longitudinal Analysis of Peripheral and Colonic CD161 + CD4 + T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation.
- Authors
Lal, Kerri G.; Phuang-Ngern, Yuwadee; Suhkumvittaya, Suchada; Leeansyah, Edwin; Alrubayyi, Aljawharah; Dias, Joana; Waickman, Adam; Kim, Dohoon; Kroon, Eugène; Pinyakorn, Suteeraporn; Eller, Leigh Anne; Maciel Jr., Milton; Rerknimitr, Rungsun; Chomchey, Nitiya; Phanuphak, Nittaya; de Souza, Mark S.; Nitayaphan, Sorachai; Ake, Julie A.; Vasan, Sandhya; Robb, Merlin L.
- 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.
- Subjects
T cell receptors; CELL populations; PRINCIPAL components analysis; T cells; PEAK load; NEUROMUSCULAR transmission; TREATMENT effectiveness; VIRAL load
- Publication
Viruses (1999-4915), 2020, Vol 12, Issue 12, p1426
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v12121426