| Expansion of HIV-specific T follicular helper cells in chronic HIV infection. | |
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MedLine Citation:
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PMID: 22922259 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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HIV targets CD4 T cells, which are required for the induction of high-affinity antibody responses and the formation of long-lived B cell memory. The depletion of antigen-specific CD4 T cells during HIV infection is therefore believed to impede the development of protective B cell immunity. Although several different HIV-related B cell dysfunctions have been described, the role of CD4 T follicular helper (TFH) cells in HIV infection remains unknown. Here, we assessed HIV-specific TFH responses in the lymph nodes of treatment-naive and antiretroviral-treated HIV-infected individuals. Strikingly, both the bulk TFH and HIV-specific TFH cell populations were significantly expanded in chronic HIV infection and were highly associated with viremia. In particular, GAG-specific TFH cells were detected at significantly higher levels in the lymph nodes compared with those of GP120-specific TFH cells and showed preferential secretion of the helper cytokine IL-21. In addition, TFH cell expansion was associated with an increase of germinal center B cells and plasma cells as well as IgG1 hypersecretion. Thus, our study suggests that high levels of HIV viremia drive the expansion of TFH cells, which in turn leads to perturbations of B cell differentiation, resulting in dysregulated antibody production. |
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Authors:
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Madelene Lindqvist; Jan van Lunzen; Damien Z Soghoian; Bjorn D Kuhl; Srinika Ranasinghe; Gregory Kranias; Michael D Flanders; Samuel Cutler; Naomi Yudanin; Matthias I Muller; Isaiah Davis; Donna Farber; Philip Hartjen; Friedrich Haag; Galit Alter; Julian Schulze zur Wiesch; Hendrik Streeck |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-08-27 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 122 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-04 Completed Date: 2012-11-19 Revised Date: 2013-04-02 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 3271-80 Citation Subset: AIM; IM |
Affiliation:
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Ragon Institute of MGH, MIT, Boston, MA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Retroviral Agents
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pharmacology,
therapeutic use B-Lymphocytes / metabolism Case-Control Studies Cell Proliferation* Cells, Cultured Chronic Disease DNA-Binding Proteins / metabolism HIV Infections / drug therapy, immunology*, pathology HIV-1 / immunology*, physiology Host-Pathogen Interactions Humans Immunoglobulin G / blood Interleukins / secretion Lymph Nodes / immunology, pathology Receptors, CXCR5 / metabolism T-Lymphocytes, Helper-Inducer / immunology*, metabolism, physiology, virology Viremia / virology |
| Grant Support | |
ID/Acronym/Agency:
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1R01-AI091450-01/AI/NIAID NIH HHS; 1R01-AI094602-01/AI/NIAID NIH HHS; R01 AI094602/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Retroviral Agents; 0/BCL6 protein, human; 0/CXCR5 protein, human; 0/DNA-Binding Proteins; 0/Immunoglobulin G; 0/Interleukins; 0/Receptors, CXCR5; 0/interleukin-21 |
| Comments/Corrections | |
Comment In:
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J Clin Invest. 2012 Sep 4;122(9):3059-62
[PMID:
22922252
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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