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Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni
Author(s) -
Blum Arthur M.,
Metwali Ahmed,
Crawford Cathy,
Li Jie,
Qadir Khurram,
Elliott David E.,
Weinstock Joel V.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fsb2fj000379
Subject(s) - microbiology and biotechnology , biology , monoclonal antibody , splenocyte , receptor , antigen , t cell , interleukin , receptor expression , western blot , t cell receptor , interleukin 2 , antibody , chemistry , cytokine , immune system , immunology , gene , biochemistry
Substance P (SP) regulates interferon‐? (IFN‐?) production through interaction with the SP receptor NK1 (SPr) on T cells at sites of inflammation. Using murine schistosomiasis, we evaluated whether SPr expression was subject to immunoregulation. Splenocytes from schistosome‐infected mice cultured for =18 h did not express SPr, as determined by quantitative polymerase chain reaction assay. However, exposure to schistosome egg antigen (SEA) for =4h induced strong receptor expression. Experiments using splenocytes fractionated with antibody‐coupled, para‐magnetic beads showed that induction localized exclusively to T cells. Receptor protein expression was confirmed with Western blot. Interleukin 12 (IL‐12) also induced strong T‐cell SPr expression. Both SEA and IL‐12 remained strong inducers of T‐cell SPr in lymphocytes from the IL‐12 (p40) and IFN‐?R doubleknockout mouse, which suggested that SEA did not require IL‐12 to induce SPr and that both worked independently of IFN‐?. Splenocytes from wild‐type mice cultured with SEA and neutralizing anti‐IL‐12 monoclonal antibody (mAb) also showed SPr induction. However, anti‐Ia mAb inhibited SEA induction of SPr. Thus, SPr is inducible on T cells. SEA induces SPr through interaction with T‐cell receptor (TCR), independently of II‐12 and IFN‐?. II‐12 induces SPr independently of TCR activation and IFN‐? expression. SP and its receptor, which regulate IFN‐? production, are probably part of the IL‐12‐Th1 circuit.—Blum, A. M., Metwali, A., Crawford, C., Li, J., Qadir, K., Elliott, D. E., Weinstock, J. V. Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni. FASEB J. 15, 950–957 (2001)