TY - JOUR
T1 - Longitudinal analysis of peripheral and colonic cd161+ cd4+ t cell dysfunction in acute hiv-1 infection and effects of early treatment initiation
AU - RV217, RV254/SEARCH010, RV304/SEARCH Study Groups
AU - Lal, Kerri G.
AU - Phuang-Ngern, Yuwadee
AU - Suhkumvittaya, Suchada
AU - Leeansyah, Edwin
AU - Alrubayyi, Aljawharah
AU - Dias, Joana
AU - Waickman, Adam
AU - Kim, Dohoon
AU - Kroon, Eugène
AU - Pinyakorn, Suteeraporn
AU - Eller, Leigh Anne
AU - Maciel, Milton
AU - Rerknimitr, Rungsun
AU - Chomchey, Nitiya
AU - Phanuphak, Nittaya
AU - de Souza, Mark S.
AU - Nitayaphan, Sorachai
AU - Ake, Julie A.
AU - Vasan, Sandhya
AU - Robb, Merlin L.
AU - Ananworanich, Jintanat
AU - Sandberg, Johan K.
AU - Schuetz, Alexandra
AU - Eller, Michael A.
AU - Paquin-Proulx, Dominic
N1 - Funding Information:
Funding: This work was funded by cooperative agreement (W81XWH-18-2-0040) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). RV254 is also supported by an intramural grant from the Thai Red Cross AIDS Research Centre. The ART in RV254 was supported by the Government Pharmaceutical Organization (Thailand), Gilead, Merck, and ViiV Healthcare. E.L. was supported by the Swedish Research Council Grant 2015-00174, Marie Skłodowska Curie Actions, Cofund, Project INCA 600398, the Jonas Söderquist Foundation for Virology and Immunology, and the Petrus and Augusta Hedlund Foundation. Further funding to J.K.S. came from the Swedish Research Council, the Swedish Cancer Society, the Hearl-Lung Foundation, and the Center for Innovative Medicine. The funding sources had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to publish.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - CD161
KW - CD4
KW - HIV-1
KW - IL-12
KW - IL-18
KW - Th17
UR - http://www.scopus.com/inward/record.url?scp=85098533567&partnerID=8YFLogxK
U2 - 10.3390/v12121426
DO - 10.3390/v12121426
M3 - Article
C2 - 33322496
AN - SCOPUS:85098533567
SN - 1999-4915
VL - 12
JO - Viruses
JF - Viruses
IS - 12
M1 - 1426
ER -