DR Non-B1 Mismatches Influence Allogeneic MLR-Induced TH1- or TH2-Like Cytokine Responses in Rhesus Monkeys
Identifieur interne : 003B79 ( Main/Exploration ); précédent : 003B78; suivant : 003B80DR Non-B1 Mismatches Influence Allogeneic MLR-Induced TH1- or TH2-Like Cytokine Responses in Rhesus Monkeys
Auteurs : A. L. Lobashevsky [États-Unis] ; P. X. Wang [États-Unis] ; J. F. George [États-Unis] ; J. Contreras [États-Unis] ; J. Townsend [États-Unis] ; J. M. Thomas [États-Unis]Source :
- Human Immunology [ 0198-8859 ] ; 1998.
English descriptors
- KwdEn :
- Teeft :
- Allele, Allogeneic, Allogeneic stimulation, Allograft, Allograft acceptance, Allograft rejection, Alloimmune responses, Allostimulation, American society, Assay, Autostimulated culture, Cell proliferation, Cell surface, Chain genes, Curr opin immunol, Cytokine, Cytokine prevalence, Cytokine production, Cytokine profile, Cytokine profiles, Cytokine response, Cytokine responses, Dendritic, Dendritic cells, Different patterns, Drb1, Early studies, Elispot, Elsevier science, Further study, Gene products, Graft, Graft rejection, Grand island, High number, Histocompatibility, Human immunol, Human immunology, Immunol, Immunol today, Immunological methods, Leukoc biol, Lobashevsky, Lymphocyte, Lymphocyte reaction, Macaque, Macaque model, Major histocompatibility, Mismatch, Molecular typing, Multiple drb1, Nonhuman primates, Normal monkey serum, Peripheral blood, Positive control, Preclinical studies, Primary alloimmune responses, Primary structure, Primates, Primer, Proc natl acad, Proinflammatory, Proliferative response, Relative response, Rhesus, Rhesus macaques, Rhesus monkeys, Significant correlation, Significant difference, Significant effect, Single cell level, Statistical analysis, Stimulation index, Transplant, Transplant center, Transplant proc, Transplant recipients, Transplantation, Transplantation immunity, Tumor necrosis, Type cytokine production, Unrelated combinations, Various numbers.
Abstract
Abstract: Human and nonhuman primates have multiple DR B1 and non-B1 alleles. However, the role of mismatched DR non-B1 alleles in primary alloimmune responses is not well understood. Macaques, which share close DNA homologies with human MHC genes and have a high number of β-chain genes in the DR subregion, are preeminent preclinical models for immunologic studies of transplant tolerance and immunosuppression. In this study, we examined the effect of allogeneic MHC Class II DRB mismatches in Th1- and Th2-like cytokine responses elicited in one-way MLR cultures in rhesus macaques. An ELISPOT method was used to estimate cytokine secretion at the single cell level. Molecular typing for DRB1 and DR non-B1 alleles was performed by a moderate-high resolution PCR-SSP method using a panel of 55 primer pairs covering 74 DRB alleles and clusters. Of 35 unrelated combinations, 66% had multiple (≥2) allelic MM at DRB1 and DR non-B1 with no significant correlation between numbers of DRB1 and DR non-B1 mismatches. Pairs with 1 or 0 MM were assigned to a mono/null MM group to obtain sufficient numbers for statistical analysis. The pairs differing by multiple vs. mono/null DRB1 MM showed no significant difference in cytokine prevalence (P = 0.69). In contrast, high IFN-γ/IL4 SFC ratios were noted in pairs with multiple vs. mono/null DR non-B1 MM (p = 0.0009). IFN-γ/IL-10 spot forming cell (SFC) ratios were consistent with IFN-γ/IL-4 SFC ratios (r = 0.98). Multiple DR non-B1 mismatches showed a trend towards higher MLR proliferative responses, although the stimulation index did not reflect the dominant cytokine response. These observations suggest a bias towards Th1-like cytokine production under allostimulation with multiple DR non-B1 gene products. Further study of the primary structure of DR non-B1 determinants may be helpful in understanding the fine molecular mechanisms governing the regulation of cytokine profiles during allostimulation in primates.
Url:
DOI: 10.1016/S0198-8859(98)00024-X
Affiliations:
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<front><div type="abstract" xml:lang="en">Abstract: Human and nonhuman primates have multiple DR B1 and non-B1 alleles. However, the role of mismatched DR non-B1 alleles in primary alloimmune responses is not well understood. Macaques, which share close DNA homologies with human MHC genes and have a high number of β-chain genes in the DR subregion, are preeminent preclinical models for immunologic studies of transplant tolerance and immunosuppression. In this study, we examined the effect of allogeneic MHC Class II DRB mismatches in Th1- and Th2-like cytokine responses elicited in one-way MLR cultures in rhesus macaques. An ELISPOT method was used to estimate cytokine secretion at the single cell level. Molecular typing for DRB1 and DR non-B1 alleles was performed by a moderate-high resolution PCR-SSP method using a panel of 55 primer pairs covering 74 DRB alleles and clusters. Of 35 unrelated combinations, 66% had multiple (≥2) allelic MM at DRB1 and DR non-B1 with no significant correlation between numbers of DRB1 and DR non-B1 mismatches. Pairs with 1 or 0 MM were assigned to a mono/null MM group to obtain sufficient numbers for statistical analysis. The pairs differing by multiple vs. mono/null DRB1 MM showed no significant difference in cytokine prevalence (P = 0.69). In contrast, high IFN-γ/IL4 SFC ratios were noted in pairs with multiple vs. mono/null DR non-B1 MM (p = 0.0009). IFN-γ/IL-10 spot forming cell (SFC) ratios were consistent with IFN-γ/IL-4 SFC ratios (r = 0.98). Multiple DR non-B1 mismatches showed a trend towards higher MLR proliferative responses, although the stimulation index did not reflect the dominant cytokine response. These observations suggest a bias towards Th1-like cytokine production under allostimulation with multiple DR non-B1 gene products. Further study of the primary structure of DR non-B1 determinants may be helpful in understanding the fine molecular mechanisms governing the regulation of cytokine profiles during allostimulation in primates.</div>
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