HLA class II associated polymorphism of interferon-gamma production - Implications for HLA-disease association
- Author(s)
- Petrovsky, N; Harrison, LC;
- Details
- Publication Year 1997-03,Volume 53,Issue #1,Page 12-16
- Journal Title
- HUMAN IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- One of several possible mechanisms for the HLA-disease association is HLA-related polymorphism of cytokine expression. However, with the exception of the tumor necrosis factors, no evidence has been found for a relationship between HLA alleles and cytokine expression. This may be because cytokine responses to commonly employed mitogens are neither antigen nor KLA dependent, and responses to recall antigens are dominated by the effect of prior antigen exposure. We reasoned that responses to alloantigens would be independent of prior antigen exposure and may therefore reveal subtle HLA-related variations in cytokine production. Here we demonstrate HLA Class II-related polymorphism of IFN-gamma production in the MLR performed between 32 subjects by a novel whole-blood method. KLA DR1, 2, and 6 were associated with high, whereas DR 3, 4, 5, and 7 were associated with low IFN-gamma production. Interestingly, DQ alleles with which these DR alleles are in linkage dysequilibrium, DQ1 and DQ2 and 3, were also associated with high and low IFN-gamma production, respectively. Ranking of HLA alleles according to whole-blood IFN-gamma production in response to mitogen or recall antigens was similar to that in the MLR, although individual allele-related differences did not reach statistical significance. TNF-or production was significantly higher in DR3-positive than in DR3-negative subjects, in accord with previous studies. These findings suggest that KLA Class II alleles, particularly at the DQ locus, or alternatively, genes in linkage with them, regulate IFN-gamma expression by T cells. The finding of HLA allele-related polymorphism of IFN-gamma production corroborates other lines of evidence that regulation of IFN-gamma expression contributes to HLA-associated susceptibility to immunoinflammatory diseases, in particular insulin-dependent diabetes and multiple sclerosis. (C) American Society for Histocompatibility and Immunogenetics, 1997.
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- NECROSIS-FACTOR-ALPHA; MONONUCLEAR-CELLS; WHOLE-BLOOD
- Publisher's Version
- https://doi.org/10.1016/S0198-8859(96)00271-6
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- Refer to copyright notice on published article.
Creation Date: 1997-03-01 12:00:00