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

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

dc.contributor.author	Miles, Brodie
dc.contributor.author	Miller, Shannon M.
dc.contributor.author	Folkvord, Joy M.
dc.contributor.author	Levy, David N.
dc.contributor.author	Rakasz, Eva G.
dc.contributor.author	Skinner, Pamela J.
dc.contributor.author	Connick, Elizabeth
dc.date.accessioned	2017-02-03T22:35:32Z
dc.date.available	2017-02-03T22:35:32Z
dc.date.issued	2016-10-07
dc.identifier.citation	Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection 2016, 12 (10):e1005924 PLOS Pathogens	en
dc.identifier.issn	1553-7374
dc.identifier.doi	10.1371/journal.ppat.1005924
dc.identifier.uri	http://hdl.handle.net/10150/622413
dc.description.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 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.
dc.description.sponsorship	NIH/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]	en
dc.language.iso	en	en
dc.publisher	PUBLIC LIBRARY SCIENCE	en
dc.relation.url	http://dx.plos.org/10.1371/journal.ppat.1005924	en
dc.rights	© 2016 Miles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.title	Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection	en
dc.type	Article	en
dc.contributor.department	Univ Arizona, Div Infect Dis	en
dc.identifier.journal	PLOS Pathogens	en
dc.description.note	Open Access Journal.	en
dc.description.collectioninformation	This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.	en
dc.eprint.version	Final published version	en
refterms.dateFOA	2018-09-11T17:25:08Z
html.description.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 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.