Cell Reports Medicine (Jun 2021)
CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions
- Laura E. Richert-Spuhler,
- Corinne M. Mar,
- Paurvi Shinde,
- Feinan Wu,
- Ting Hong,
- Evan Greene,
- Sharon Hou,
- Katherine Thomas,
- Raphael Gottardo,
- Nelly Mugo,
- Guy de Bruyn,
- Connie Celum,
- Jared M. Baeten,
- Jairam R. Lingappa,
- Jennifer M. Lund,
- Connie Celum,
- Anna Wald,
- Jairam R. Lingappa,
- Jared M. Baeten,
- Mary S. Campbell,
- Lawrence Corey,
- Robert W. Coombs,
- James P. Hughes,
- Amalia Magaret,
- M. Juliana McElrath,
- Rhoda Morrow,
- James I. Mullins,
- David Coetzee,
- Kenneth Fife,
- Edwin Were,
- Max Essex,
- Joseph Makhema,
- Elly Katabira,
- Allan Ronald,
- Elizabeth Bukusi,
- Craig Cohen,
- Saidi Kapiga,
- Rachel Manongi,
- Carey Farquhar,
- Grace John-Stewart,
- James Kiarie,
- Sinead Delany-Moretlwe,
- Helen Rees,
- Guy de Bruyn,
- Glenda Gray,
- James McIntyre,
- Nelly Rwamba Mugo,
- Connie Celum,
- Jared M. Baeten,
- Deborah Donnell,
- Robert W. Coombs,
- Lisa Frenkel,
- Craig W. Hendrix,
- Jairam R. Lingappa,
- M. Juliana McElrath,
- Kenneth Fife,
- Edwin Were,
- Elioda Tumwesigye,
- Patrick Ndase,
- Elly Katabira,
- Allan Ronald,
- Eliabeth Bukusi,
- Craig Cohen,
- Jonathan Wangisi,
- James Campbell,
- Jordan Tappero,
- James Kiarie,
- Carey Farquhar,
- Grace John-Stewart,
- Nelly Rwamba Mugo
Affiliations
- Laura E. Richert-Spuhler
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Corinne M. Mar
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- Paurvi Shinde
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Feinan Wu
- Genomics & Bioinformatics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Ting Hong
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- Evan Greene
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Sharon Hou
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- Katherine Thomas
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- Raphael Gottardo
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- Nelly Mugo
- Department of Global Health, University of Washington, Seattle, WA 98104, USA; Kenya Medical Research Institute, Nairobi, Kenya
- Guy de Bruyn
- Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa
- Connie Celum
- Department of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Medicine, University of Washington, Seattle, WA 98104, USA; Department of Epidemiology, University of Washington, Seattle, WA 98104, USA
- Jared M. Baeten
- Department of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Medicine, University of Washington, Seattle, WA 98104, USA; Department of Epidemiology, University of Washington, Seattle, WA 98104, USA
- Jairam R. Lingappa
- Department of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Medicine, University of Washington, Seattle, WA 98104, USA; Department of Pediatrics, University of Washington, Seattle, WA 98104, USA; Corresponding author
- Jennifer M. Lund
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98104, USA; Corresponding author
- Connie Celum
- Anna Wald
- Jairam R. Lingappa
- Jared M. Baeten
- Mary S. Campbell
- Lawrence Corey
- Robert W. Coombs
- James P. Hughes
- Amalia Magaret
- M. Juliana McElrath
- Rhoda Morrow
- James I. Mullins
- David Coetzee
- Kenneth Fife
- Edwin Were
- Max Essex
- Joseph Makhema
- Elly Katabira
- Allan Ronald
- Elizabeth Bukusi
- Craig Cohen
- Saidi Kapiga
- Rachel Manongi
- Carey Farquhar
- Grace John-Stewart
- James Kiarie
- Sinead Delany-Moretlwe
- Helen Rees
- Guy de Bruyn
- Glenda Gray
- James McIntyre
- Nelly Rwamba Mugo
- Connie Celum
- Jared M. Baeten
- Deborah Donnell
- Robert W. Coombs
- Lisa Frenkel
- Craig W. Hendrix
- Jairam R. Lingappa
- M. Juliana McElrath
- Kenneth Fife
- Edwin Were
- Elioda Tumwesigye
- Patrick Ndase
- Elly Katabira
- Allan Ronald
- Eliabeth Bukusi
- Craig Cohen
- Jonathan Wangisi
- James Campbell
- Jordan Tappero
- James Kiarie
- Carey Farquhar
- Grace John-Stewart
- Nelly Rwamba Mugo
- Journal volume & issue
-
Vol. 2,
no. 6
p. 100322
Abstract
Summary: 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.
