Impact of class A, B and C CpG-oligodeoxynucleotides on in vitro activation of innate immune cells in human immunodeficiency virus-1 infected individuals.
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-alpha (IFN-alpha) 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.
Martinson
Jeffrey A
JA
Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
Tenorio
Allan R
AR
Montoya
Carlos J
CJ
Al-Harthi
Lena
L
Gichinga
Carolyne N
CN
Krieg
Arthur M
AM
Baum
Linda L
LL
Landay
Alan L
AL
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D016898:Interferon-alpha / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology; D019562:Viral Load
C408982:CPG-oligonucleotide; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9