Session Information
Session Title: T-cell Biology and Targets in Autoimmune Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Differentiation of naïve CD4+ T cells is considered to be an irreversible event and, in particular, the plasticity is thought to be completely lost in Th1 subset in vitro after multiple stimulations. Superantigens produced by different types of pathogens have been linked to autoimmune diseases. Superantigen-stimulation does not prime an adaptive immune response but causes a massive production of cytokines by CD4+ T cells. We hypothesized that superantigens are capable of stimulating Th1 cells to produce inflammatory cytokine, IL-17.
Methods:
MOG35-55-specific and herpes simplex virus (HSV)-specific CD4+ T cell clones were established from PBMC of healthy individuals. These CD4+ T cell clones were stimulated by each antigen respectively under Th17 polarizing conditions (with addition of IL-1, IL-6, TGF-beta, anti-IL-12 and anti-IFN-ƒngamma) or cultured with bacterial superantigens, SEB or TSST-1. IL-17 and IFN-gamma production was determined by ELISA, double-color ELISPOT and intracellular cytokine staining.
Results:
Upon repeated Ag-specific stimulation, Th1 clones proliferated specifically to MOG35-55 and HSV respectively and produced IFN-gamma and IL-2, but did not produce IL-17. Various Th17-polarization conditions including co-stimulation with IL-1, TNF, IL-6, IL-23, TGF-beta in combination with anti-IL-12 and anti-IFN-gamma antibodies did not induce measurable IL-17 from these Th1 clones. However, superantigen-stimulation promoted both clones to produce IL-17 at a range of 0.5 – 1 ng/1×105 cells. Combination of SEB and TSST-1 showed additive effect on IL-17 production by Th1 clone cells where IL-17 level was greater than 2 ng/1×105 cells. Using double-color ELISPOT assay, we found 30% of IFN-gamma-producing cells were positive for IL-17, suggests that superantigens promoted IL-17 production from highly polarized Th1 cloned cells. Interestingly, IL-17 production by these Th1 clones was blocked by anti-HLA class II or anti-TCR alpha/beta chain antibodies.
Conclusion:
We have demonstrated that highly polarized Th1 clones can produce a significant amount of IL-17 in response to superantigen stimulation. Infections have been linked to exacerbation of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Stimulating Th1 cells to produce IL-17 by superantigens of infecting pathogens may be responsible.
Disclosure:
K. Yomogida,
None;
Y. K. Chou,
None;
C. Q. Chu,
None.
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