1. T cell substance P receptor governs antigen-elicited IFN-[gamma] production
- Author
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Blum, Arthur M., Metwali, Ahmed, Elliott, David E., and Weinstock, Joel V.
- Subjects
T cells -- Physiological aspects ,Neuropeptides -- Physiological aspects ,Inflammation -- Physiological aspects ,Granuloma -- Physiological aspects ,Schistosomiasis -- Physiological aspects ,Substance P -- Physiological aspects ,Mice -- Physiological aspects ,Biological sciences - Abstract
Substance P (SP) enhances antigen-dependent T cell IFN-[gamma] production. It was determined if a T cell neurokinin-1 receptor (NK-1R) was critical for IFN-[gamma] regulation. T cells from schistosome-infected mice were mixed with splenocytes from uninfected NK-1R knockout (KO) animals. Thus only the schistosome egg antigen-specific T cells expressed NK-1R. The cells were cultured 18 h with or without SP. SP enhanced antigen-induced IFN-[gamma] production fourfold without affecting IL-4 or IL-5 secretion. NK-1R inhibitor blocked this stimulation. Neither purified T cells nor naive KO splenocytes cultured alone responded to antigen. To further define the importance of T cell NK-1R, we developed a T cell-selective NK-1R KO mouse by reconstituting T cell-deficient Rag mice with NK-1R KO T cells. These mice challanged with schistosomiasis developed abnormal liver granulomas. Granuloma size was smaller in T cell-selective NK-1R KO mice compared with granulomas in Rag reconstituted with normal T cells. Splenocytes and granuloma cells from NK-1R KO mice made less IFN-[gamma]. The mice also made less IgG2a. Thus T cell NK-1R is important for IFN-[gamma] regulation. neuropeptides; inflammation; granuloma; neurokinin 1 receptor; schistosomiasis
- Published
- 2003