title: Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection.
abstract: During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells. CD8 TFR modestly limit HIV replication in follicular helper T cells (TFH), impair TFH IL-21 production via Tim-3, and inhibit IgG production by B cells during ex vivo HIV infection. CD8 TFR induce TFH apoptosis through HLA-E, but induce less apoptosis than conventional CD8 T cells. These data demonstrate that a unique regulatory CD8 population exists in follicles that impairs GC function in HIV infection.
authors.affiliation: Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver, Colorado, United States of America.
authors.forename: Brodie
authors.identifier: http://orcid.org/0000-0002-5670-4432
authors.initials: B
authors.lastname: Miles
authors.affiliation: Department of Immunology and Microbiology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Colorado, United States of America.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Miller
authors.affiliation: Division of Infectious Diseases, University of Arizona, Arizona, United States of America.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Folkvord
authors.affiliation: Department of Basic Science, New York University College of Dentistry, New York, United States of America.
authors.forename: David N
authors.initials: DN
authors.lastname: Levy
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Wisconsin, United States of America.
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, United States of America.
authors.forename: Pamela J
authors.identifier: http://orcid.org/0000-0003-3388-1687
authors.initials: PJ
authors.lastname: Skinner
authors.affiliation: Division of Infectious Diseases, University of Arizona, Arizona, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Connick
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D014066:Palatine Tonsil / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*