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

PLoS Pathog. 2016 Oct 7;12(10):e1005924. doi: 10.1371/journal.ppat.1005924. eCollection 2016 Oct.

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.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Coculture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Germinal Center / immunology*
  • HIV Infections / immunology*
  • Humans
  • Macaca mulatta
  • Palatine Tonsil / immunology
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • T-Lymphocyte Subsets / immunology*