CpG oligonucleotides induce strong humoral but only weak CD4+ T cell responses to protein antigens in rhesus macaques in vivo

Hartmann, Gunther; Marschner, Anja; Viveros, Pablo Renner; Stahl–Hennig∥, Christiane; Eisenblätter, Martin; Suh, You-Suk; Endres, Stefan; Tenner-Rácz, Klara; Überla, Klaus; Rácz, Paul; Steinman, Ralph M.; Ignatius, Ralf

doi:10.1016/j.vaccine.2005.01.077

Cited by 21 publications

(18 citation statements)

References 30 publications

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“…In contrast with mice, CpG DNA does not support priming of Th cell responses in primates (45). One could speculate that this defect in priming Th cell responses is due to the failure of CpG DNA to directly induce IL-12p70 in human myeloid cells.…”

Section: Discussionmentioning

confidence: 89%

T Cell-Independent, TLR-Induced IL-12p70 Production in Primary Human Monocytes

Bekeredjian‐Ding¹,

Roth

Gilles

et al. 2006

The Journal of Immunology

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102

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IL-12p70 is a key cytokine for the induction of Th1 immune responses. IL-12p70 production in myeloid cells is thought to be strictly controlled by T cell help. In this work we demonstrate that primary human monocytes can produce IL-12p70 in the absence of T cell help. We show that human monocytes express TLR4 and TLR8 but lack TLR3 and TLR7 even after preincubation with type I IFN. Simultaneous stimulation of TLR4 and TLR8 induced IL-12p70 in primary human monocytes. IL-12p70 production in peripheral blood myeloid dendritic cells required combined stimulation of TLR7/8 ligands together with TLR4 or with TLR3 ligands. In the presence of T cell-derived IL-4, but not IFN-γ, stimulation with TLR7/8 ligands was sufficient to stimulate IL-12p70 production. In monocytes, type I IFN was required but not sufficient to costimulate IL-12p70 induction by TLR8 ligation. Furthermore, TLR8 ligation inhibited LPS-induced IL-10 in monocytes, and LPS alone gained the ability to stimulate IL-12p70 in monocytes when the IL-10 receptor was blocked. Together, these results demonstrate that monocytes are licensed to synthesize IL-12p70 through type I IFN provided via the Toll/IL-1R domain-containing adaptor inducing IFN-β pathway and the inhibition of IL-10, both provided by combined stimulation with TLR4 and TLR8 ligands, triggering a potent Th1 response before T cell help is established.

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Section: Discussionmentioning

confidence: 89%

T Cell-Independent, TLR-Induced IL-12p70 Production in Primary Human Monocytes

Bekeredjian‐Ding¹,

Roth

Gilles

et al. 2006

The Journal of Immunology

Self Cite

102

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“…CpG ODNs have successfully stimulated protective innate immune responses against Leishmania amazonensis and Leishmania major in both simian immunodeficiency virus-infected and healthy rhesus macaques (3,10). CpG ODN induction of IP-10 in rhesus macaques has been demonstrated in vitro (1,5,9) and in one instance in vivo, when a hepatitis B vaccine was adjuvanted with CpG ODN 7909 (5). We conclude that safety and immune responses to CpG 7909 in the rhesus macaque may prove to be a useful model of human responses to CpG 7909 and may eventually be used to validate IP-10 as a biomarker of innate immune system activation against pathogens.…”

Section: Discussionmentioning

confidence: 99%

Activation of Innate Immunity in Healthy Macaca mulatta Macaques by a Single Subcutaneous Dose of GMP CpG 7909: Safety Data and Interferon-Inducible Protein-10 Kinetics for Humans and Macaques

Stewart

McGrath

Krieg

et al. 2008

Clin Vaccine Immunol

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“…This result, coupled with our findings, may provide an impetus for the reporting of macaque origins in pathogenesis studies and spur research into the functional consequences of these regional differences. Currently, macaque origins are rarely specified in methods sections of immunology and pathogenesis publications (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54), though this data may be profoundly influential.…”

Section: Discussionmentioning

confidence: 99%

Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques

Krebs

Jin

Rudersdorf

et al. 2005

The Journal of Immunology

106

116

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Acute shortages of Indian origin Rhesus macaques significantly hinder HIV/AIDS research. Cellular immune responses are particularly difficult to study because only a subset of animals possess MHC class I (MHC I) alleles with defined peptide-binding specificities. To expand the pool of nonhuman primates suitable for studies of cellular immunity, we defined 66 MHC I alleles in Cynomolgus macaques (Macaca fascicularis) of Chinese, Vietnamese, and Mauritian origin. Most MHC I alleles were found only in animals from a single geographic origin, suggesting that Cynomolgus macaques from different origins are not interchangeable in studies of cellular immunity. Animals from Mauritius may be particularly valuable because >50% of these Cynomolgus macaques share the MHC class I allele combination Mafa-B*430101, Mafa-B*440101, and Mafa-B*460101. The increased MHC I allele sharing of Mauritian origin Cynomolgus macaques may dramatically reduce the overall number of animals needed to study cellular immune responses in nonhuman primates while simultaneously reducing the confounding effects of genetic heterogeneity in HIV/AIDS research.

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CpG oligonucleotides induce strong humoral but only weak CD4+ T cell responses to protein antigens in rhesus macaques in vivo

Cited by 21 publications

References 30 publications

T Cell-Independent, TLR-Induced IL-12p70 Production in Primary Human Monocytes

T Cell-Independent, TLR-Induced IL-12p70 Production in Primary Human Monocytes

Activation of Innate Immunity in Healthy Macaca mulatta Macaques by a Single Subcutaneous Dose of GMP CpG 7909: Safety Data and Interferon-Inducible Protein-10 Kinetics for Humans and Macaques

Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques

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