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Am J Physiol Gastrointest Liver Physiol 284: G197-G204, 2003. First published October 2, 2002; doi:10.1152/ajpgi.00271.2002
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Vol. 284, Issue 2, G197-G204, February 2003

T cell substance P receptor governs antigen-elicited IFN-gamma production

Arthur M. Blum, Ahmed Metwali, David E. Elliott, and Joel V. Weinstock

Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242

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 naïve 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





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