Expansion of HIV-specific T follicular helper cells in chronic HIV infection.
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Expansion of HIV-specific T follicular helper cells in chronic HIV infection. / Lindqvist, Madelene; van Lunzen, Jan; Soghoian, Damien Z; Kuhl, Bjorn D; Ranasinghe, Srinika; Kranias, Gregory; Flanders, Michael D; Cutler, Samuel; Yudanin, Naomi; Muller, Matthias I; Davis, Isaiah; Farber, Donna; Hartjen, Philip; Haag, Friedrich; Alter, Galit; Schulze Zur Wiesch, Julian; Streeck, Hendrik.
in: J CLIN INVEST, Jahrgang 122, Nr. 9, 9, 2012, S. 3271-3280.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Expansion of HIV-specific T follicular helper cells in chronic HIV infection.
AU - Lindqvist, Madelene
AU - van Lunzen, Jan
AU - Soghoian, Damien Z
AU - Kuhl, Bjorn D
AU - Ranasinghe, Srinika
AU - Kranias, Gregory
AU - Flanders, Michael D
AU - Cutler, Samuel
AU - Yudanin, Naomi
AU - Muller, Matthias I
AU - Davis, Isaiah
AU - Farber, Donna
AU - Hartjen, Philip
AU - Haag, Friedrich
AU - Alter, Galit
AU - Schulze Zur Wiesch, Julian
AU - Streeck, Hendrik
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Humans
KW - Cells, Cultured
KW - Chronic Disease
KW - Case-Control Studies
KW - Cell Proliferation
KW - DNA-Binding Proteins/metabolism
KW - Immunoglobulin G/blood
KW - Viremia/virology
KW - Anti-Retroviral Agents/pharmacology/therapeutic use
KW - B-Lymphocytes/metabolism
KW - HIV Infections/drug therapy/immunology/pathology
KW - HIV-1/immunology/physiology
KW - Host-Pathogen Interactions
KW - Interleukins/secretion
KW - Lymph Nodes/immunology/pathology
KW - Receptors, CXCR5/metabolism
KW - T-Lymphocytes, Helper-Inducer/immunology/metabolism/physiology/virology
KW - Humans
KW - Cells, Cultured
KW - Chronic Disease
KW - Case-Control Studies
KW - Cell Proliferation
KW - DNA-Binding Proteins/metabolism
KW - Immunoglobulin G/blood
KW - Viremia/virology
KW - Anti-Retroviral Agents/pharmacology/therapeutic use
KW - B-Lymphocytes/metabolism
KW - HIV Infections/drug therapy/immunology/pathology
KW - HIV-1/immunology/physiology
KW - Host-Pathogen Interactions
KW - Interleukins/secretion
KW - Lymph Nodes/immunology/pathology
KW - Receptors, CXCR5/metabolism
KW - T-Lymphocytes, Helper-Inducer/immunology/metabolism/physiology/virology
M3 - SCORING: Journal article
VL - 122
SP - 3271
EP - 3280
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 9
M1 - 9
ER -
