Document Detail

Expansion of HIV-specific T follicular helper cells in chronic HIV infection.
MedLine Citation:
PMID:  22922259     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-27
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-04     Completed Date:  2012-11-19     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3271-80     Citation Subset:  AIM; IM    
Ragon Institute of MGH, MIT, Boston, MA, USA.
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MeSH Terms
Anti-Retroviral Agents / 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
Immunoglobulin G / blood
Interleukins / secretion
Lymph Nodes / immunology,  pathology
Receptors, CXCR5 / metabolism
T-Lymphocytes, Helper-Inducer / immunology*,  metabolism,  physiology,  virology
Viremia / virology
Grant Support
1R01-AI091450-01/AI/NIAID NIH HHS; 1R01-AI094602-01/AI/NIAID NIH HHS; R01 AI091450/AI/NIAID NIH HHS; R01 AI094602/AI/NIAID NIH HHS
Reg. No./Substance:
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
Comment In:
J Clin Invest. 2012 Sep 4;122(9):3059-62   [PMID:  22922252 ]

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