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Inadequate T follicular cell help impairs B cell immunity during HIV infection
- Source :
- Nature Medicine. April 1, 2013, Vol. 19 Issue 4, p494, 8 p.
- Publication Year :
- 2013
-
Abstract
- The majority of HIV-infected individuals fail to produce protective antibodies and have diminished responses to new immunizations (1-3). We report here that even though there is an expansion of follicular helper T ([T.sub.FH]) cells in HIV-infected individuals, the cells are unable to provide adequate B cell help. We found a higher frequency of programmed cell death ligand 1 ([PD-L1).sup.+] germinal center B cells from lymph nodes of HIV-infected individuals suggesting a potential role for PD-1-PD-L1 interaction in regulating [T.sub.FH] cell function. In fact, we show that engagement of PD-1 on [T.sub.FH] cells leads to a reduction in cell proliferation, activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine secretion. Blocking PD-1 signaling enhances HIV-specific immunoglobulin production in vitro. We further show that at least part of this defect involves IL-21, as addition of this cytokine rescues antibody responses and plasma cell generation in vitro. Our results suggest that deregulation of [T.sub.FH] cell-mediated B cell help diminishes B cell responses during HIV infection and may be related to PD-1 triggering on [T.sub.FH] cells. These results demonstrate a role for [T.sub.FH] cell impairment in HIV pathogenesis and suggest that enhancing their function could have a major impact on the outcome and control of HIV infection, preventing future infections and improving immune responses to vaccinations.<br />During HIV infection there is a profound deregulation in B cell function (4-6). However, little is known about the underlying mechanisms that alter B cell responses and antibody production at [...]
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 19
- Issue :
- 4
- Database :
- Gale General OneFile
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.326982669
- Full Text :
- https://doi.org/10.1038/nm.3109