@article{e0d800d22fd2403d9b5ab65d13fe8e5a,
title = "CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions",
abstract = "We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.",
keywords = "CD101, HIV acquisition, T cell, host genetic variation, immune quiescence, inflammation, inflammatory homeostasis",
author = "{for the Partners in Prevention HSV/HIV Transmission Study} and {and the Partners PrEP Study Teams} and Richert-Spuhler, {Laura E.} and Mar, {Corinne M.} and Paurvi Shinde and Feinan Wu and Ting Hong and Evan Greene and Sharon Hou and Katherine Thomas and Raphael Gottardo and Nelly Mugo and {de Bruyn}, Guy and Connie Celum and Baeten, {Jared M.} and Lingappa, {Jairam R.} and Lund, {Jennifer M.} and Anna Wald and Campbell, {Mary S.} and Lawrence Corey and Coombs, {Robert W.} and Hughes, {James P.} and Amalia Magaret and McElrath, {M. Juliana} and Rhoda Morrow and Mullins, {James I.} and David Coetzee and Kenneth Fife and Edwin Were and Max Essex and Joseph Makhema and Elly Katabira and Allan Ronald and Elizabeth Bukusi and Craig Cohen and Saidi Kapiga and Rachel Manongi and Carey Farquhar and Grace John-Stewart and James Kiarie and Sinead Delany-Moretlwe and Helen Rees and Glenda Gray and James McIntyre and Mugo, {Nelly Rwamba} and Deborah Donnell and Lisa Frenkel and Hendrix, {Craig W.} and Elioda Tumwesigye and Patrick Ndase and Eliabeth Bukusi and Jonathan Wangisi",
note = "Funding Information: We thank Lucia Vojtech at the University of Washington for advice regarding EBV stimulation assays and Alyssa Dawson and Dolores Covarrubias in the Genomics Shared Resources at Fred Hutchinson Cancer Research Center for library preparation and RNA sequencing. Funding was provided by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI129715 to J.R.L. R01 AI131914 to J.M.L. and J.R.L. R21 AI127156 to J.R.L. and J.M.L. T32 AI007140 to L.E.R.-S. and P30 AI027757 to J.M.B.) and by the Bill and Melinda Gates Foundation (grant 47674). Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. In addition, this research was supported by the Genomics & Bioinformatics Shared Resource of the Fred Hutch/University of Washington Cancer Consortium (P30 CA015704) and an American Association of Immunologists career reentry fellowship (to L.E.R.-S.). Data management was provided by DF/Net Research, and site laboratory oversight was provided by Contract Laboratory Services (University of the Witwatersrand, Johannesburg, South Africa). Study medication in the Partners PrEP Study was donated by Gilead Sciences. We thank the participants in these studies for their dedication and commitment. L.E.R.-S. and P.S. performed experiments, acquired data, and performed data analyses. E.G. and R.G. conceived the FAUST analysis method and performed FAUST data analysis. C.M.M. F.W. T.H. S.H. and K.T. performed data curation/management and/or statistical analysis. N.M. G.d.B. C.C. J.M.B. and J.R.L. conducted the clinical trial from which samples for this study were provided and/or provided study supervision. L.E.R.-S. J.R.L. and J.M.L. designed the research study and supervised completion of the experiments. L.E.R.-S. J.R.L. and J.M.L. wrote the first draft of the manuscript, and all authors provided editorial contribution and approved the final draft. All data analysis conducted by E.G. and R.G. were completed while E.G. was a full-time employee of the Fred Hutchinson Cancer Research Center. E.G. declares ownership interest in Ozette Technologies. R.G. has received consulting income from Takeda Vaccines, speaker fees from Illumina and Fluidigm, and research support from Janssen Pharmaceuticals and declares ownership in Ozette Technologies. Funding Information: We thank Lucia Vojtech at the University of Washington for advice regarding EBV stimulation assays and Alyssa Dawson and Dolores Covarrubias in the Genomics Shared Resources at Fred Hutchinson Cancer Research Center for library preparation and RNA sequencing. Funding was provided by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health ( R01 AI129715 to J.R.L., R01 AI131914 to J.M.L. and J.R.L., R21 AI127156 to J.R.L. and J.M.L., T32 AI007140 to L.E.R.-S., and P30 AI027757 to J.M.B.) and by the Bill and Melinda Gates Foundation (grant 47674 ). Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. In addition, this research was supported by the Genomics & Bioinformatics Shared Resource of the Fred Hutch/University of Washington Cancer Consortium ( P30 CA015704 ) and an American Association of Immunologists career reentry fellowship (to L.E.R.-S.). Data management was provided by DF/Net Research, and site laboratory oversight was provided by Contract Laboratory Services (University of the Witwatersrand, Johannesburg, South Africa). Study medication in the Partners PrEP Study was donated by Gilead Sciences. We thank the participants in these studies for their dedication and commitment. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jun,
day = "15",
doi = "10.1016/j.xcrm.2021.100322",
language = "English (US)",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "6",
}