Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni

Substance P (SP) regulates interferon-gamma (IFN-gamma) production through interaction with the SP receptor NK1 (SPr) on T cells at sites of inflammat ion. Using murine schistosomiasis, we evaluated whether SPr expression was subject to immunoregulation. Splenocytes from schistosome-infected mice cul tured for less than or equal to 18 h did not express SPr, as determined by quantitative polymerase chain reaction assay. However, exposure to schistos ome egg antigen (SEA) for less than or equal to4 h induced strong receptor expression. Experiments using splenocytes fractionated with antibody-couple d, paramagnetic beads showed that induction localized exclusively to T cell s. Receptor protein expression was confirmed with Western blot. Interleukin 12 (IL-12) also induced strong T-cell SPr expression. Both SEA and IL-12 r emained strong inducers of T-cell SPr in lymphocytes from the IL-12 (p40) a nd IFN-gammaR doublel-knockout mouse, which suggested that SEA did not requ ire IL-12 to induce SPr and that both worked independently of IFN-gamma. Sp lenocytes 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 ind uces SPr through interaction with T-cell receptor (TCR), independently of I L-12 and IFN-gamma. IL-12 induces SPr independently of TCR activation and I FN-gamma expression. SP and its receptor, which regulate IFN-gamma producti on, are probably part of the IL-12-Th1 circuit.