Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection
Miller, Shannon M.
Folkvord, Joy M.
Levy, David N.
Rakasz, Eva G.
Skinner, Pamela J.
AffiliationUniv Arizona, Div Infect Dis
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationFollicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection 2016, 12 (10):e1005924 PLOS Pathogens
Rights© 2016 Miles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
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AbstractDuring 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.
NoteOpen Access Journal.
VersionFinal published version
SponsorsNIH/NIAID [R01 AI096966, R01 AI078783A, T32 AI007447-22, T32 AI007405]; Wisconsin National Primate Research Center (WNPRC) [P51OD011106]; Tim Gill Fund; University of Colorado Denver Division of Infectious Diseases; Cancer Center Support Grant [P30CA046934]; Skin Diseases Research Cores Grant [P30AR057212]; NIH [R25OD010487]