Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection.
Brodie MilesShannon M MillerJoy M FolkvordDavid N LevyEva G RakaszPamela J SkinnerElizabeth ConnickPublished in: PLoS pathogens (2016)
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.
Keyphrases
- antiretroviral therapy
- regulatory t cells
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv aids
- dendritic cells
- nk cells
- endoplasmic reticulum stress
- hepatitis c virus
- poor prognosis
- cell death
- hiv testing
- cell proliferation
- cell cycle arrest
- long non coding rna
- electronic health record
- mass spectrometry
- signaling pathway
- men who have sex with men
- high resolution
- anti inflammatory