Open AccessFollicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection
Author(s) -
MJ Brodie,
Shan M. Miller,
Joy M. Folkvord,
David Levy,
Eva G. Rakasz,
Pamela J. Skinner,
Elizabeth Connick
Publication year - 2016
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1005924
Subject(s) - cytotoxic t cell , biology , cd8 , germinal center , ex vivo , interleukin 21 , immunology , microbiology and biotechnology , immune system , virology , in vivo , antibody , in vitro , b cell , genetics
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 CXCR5 hi CD44 hi CD8 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 T FR ), 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 T FR modestly limit HIV replication in follicular helper T cells (T FH ), impair T FH IL-21 production via Tim-3, and inhibit IgG production by B cells during ex vivo HIV infection. CD8 T FR induce T FH 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.