Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection

Brodie Miles, Shannon M. Miller, Joy M. Folkvord, David N. Levy, Eva G. Rakasz, Pamela J. Skinner, Elizabeth Connick

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere1005924
JournalPLoS Pathogens
Volume12
Issue number10
DOIs
StatePublished - Oct 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Miles, B., Miller, S. M., Folkvord, J. M., Levy, D. N., Rakasz, E. G., Skinner, P. J., & Connick, E. (2016). Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection. PLoS Pathogens, 12(10), [e1005924]. https://doi.org/10.1371/journal.ppat.1005924