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Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
1Correspondence: Division of Gastroenterology (4607 JCP), University of Iowa Hospital and Clinics, 200 Hawkins Drive, Iowa City, IA 52242-1009, USA. E-mail: joel-weinstock{at}uiowa.edu
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 4 h induced strong
receptor expression. Experiments using splenocytes fractionated with
antibody-coupled, paramagnetic 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 double-knockout 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 IL-12 and
IFN-. IL-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.
Key Words: schistosomiasis • substance P • substance P receptor • IL-12 • schistosome egg antigen
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