CpG oligonucleotides enhance proliferative and effector responses of B Cells in HIV-infected individuals.
Stimulation through TLR represents a new therapeutic approach for enhancing Ab responses to vaccination. Considering that Ab responses are decreased in HIV disease and that B cells express TLR9 and respond to TLR9 agonists, we investigated the responsiveness of B cell subpopulations from HIV-infected and uninfected individuals to the TLR9 agonist CpG oligonucleotide type B (CpG-B) in the presence and absence of BCR ligation and T cell help (CD40L). CpG-B was equally effective in stimulating the proliferation of naive B cells of HIV-infected individuals and HIV-negative individuals, and, when combined with BCR and CD40 ligation, cytokine secretion by naive B cells was also comparable in HIV-infected and uninfected individuals. In contrast, CD27(+) memory/activated B cells of HIV-infected individuals with active disease were less responsive to CpG-B in terms of proliferation and cytokine secretion when compared with CD27(+) B cells of HIV-negative and HIV-infected individuals whose viremia was controlled by antiretroviral therapy. These findings suggest that despite abnormalities in memory B cells of HIV-infected individuals with active disease, naive B cells of HIV-infected individuals, irrespective of disease status, can respond to TLR9 agonists and that the incorporation of such agents in vaccine formulations may enhance their Ab responses to vaccination.
Malaspina
Angela
A
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. amalaspina@niaid.nih.gov
Moir
Susan
S
DiPoto
Angela C
AC
Ho
Jason
J
Wang
Wei
W
Roby
Gregg
G
O'Shea
Marie A
MA
Fauci
Anthony S
AS
D000276:Adjuvants, Immunologic; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006678:HIV; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9