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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/622413 |
| Date | 07 October 2016 |
| Creators | Miles, Brodie, Miller, Shannon M., Folkvord, Joy M., Levy, David N., Rakasz, Eva G., Skinner, Pamela J., Connick, Elizabeth |
| Contributors | Univ Arizona, Div Infect Dis |
| Publisher | PUBLIC LIBRARY SCIENCE |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2016 Miles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. |
| Relation | http://dx.plos.org/10.1371/journal.ppat.1005924 |
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