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Impact of class A, B and C CpG‐oligodeoxynucleotides on in vitro activation of innate immune cells in human immunodeficiency virus‐1 infected individuals
Author(s) -
Martinson Jeffrey A.,
Tenorio Allan R.,
Montoya Carlos J.,
AlHarthi Lena,
Gichinga Carolyne N.,
Krieg Arthur M.,
Baum Linda L.,
Landay Alan L.
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02530.x
Subject(s) - tlr9 , cpg oligodeoxynucleotide , biology , immunology , innate immune system , cpg site , cd86 , immune system , cd40 , cd80 , peripheral blood mononuclear cell , interferon , virology , cytotoxic t cell , t cell , in vitro , dna methylation , gene expression , biochemistry , gene
Summary Oligodeoxynucleotides (ODN) with unmethylated deoxycytidyl‐deoxyguanosine dinucleotides (CpG‐ODNs) stimulate Toll‐like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDC) and B cells and activate innate and adaptive immunity. Three classes of synthetic CpG‐ODNs, class A, B and C, activate cells through TLR9; our goal was to evaluate their effect on cells from human immunodeficiency virus (HIV)‐1 + individuals. We compared the frequencies and the unstimulated activation status of immune effector cells in HIV‐1 + and HIV‐1 – individuals. Fewer pDC, myeloid dendritic cells (mDC), B cells, natural killer (NK) cells and invariant natural killer T cells (iNKT) were present in HIV‐1 + peripheral blood mononuclear cells (PBMC) and their baseline activation status was higher than HIV‐1 – PBMC. Exposure of HIV‐1 + PBMC to all classes of CpG‐ODNs led to activation and maturation of pDC based on CD86, CD80, and CD83 expression similar to that of cells from HIV‐1 – individuals. The percentage of CpG‐ODN stimulated pDC that express CD40 was dramatically higher when cells were obtained from HIV‐1 + than from HIV‐1 – individuals. B‐lymphocytes were activated similarly in HIV‐1 + and HIV‐1 – individuals. mDC, NK and iNKT cell, which lack TLR9, were indirectly activated. Interferon‐α (IFN‐α) and interferon inducible protein 10 (IP‐10) secretion was induced by class A or C but not class B CpG‐ODN, but the concentrations were less than those produced by HIV‐1 – PBMC. HIV‐1 infected individuals have fewer innate effector cells that are chronically activated, but these cells can be further activated by CpG‐ODN, which suggests that synthetic CpG‐ODNs could be used to enhance the immune system in HIV‐1 infected individuals.