Neuromuscular regulation of T-cell activation.
Recent investigations in our laboratory have shown that murine intestinal smooth muscle cells (ISMCs) can exert an immunomodulatory effect on T-cells. Therefore, we examined the effects of substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) on the ability of ISMCs to modulate T-cell proliferation and lymphokine generation. T-cell proliferation was observed when these cells were co-cultured with IFN-pretreated C57/BL6 ISMCs which expressed major histocompatibility complex II (MHC II), but not during T-cell co-culture with C2D (MHC II -/-) ISMCs pretreated in the same manner. T-cell proliferation during co-culture with C57/BL6 ISMCs was also associated with significantly enhanced T-cell synthesis of IFN. When CGRP (at 10(-9) M), but not substance P or VIP, was added to C57/BL6 ISMCs during the IFN-pretreatment period. T-cell proliferation was significantly increased. However, increased T-cell proliferation was not observed if the concentration of CGRP was increased to 10(-6) M. At the higher concentration, addition of substance P or VIP during the pretreatment period significantly inhibited the subsequent T-cell proliferation. Pretreatment of C57/BL6 ISMCs with any of the three neuropeptides and IFN resulted in the diminished production of IL-4 and IFN by co-cultured T-cells. A similar pattern of cytokine secretion was observed during T-cell co-culture with IFN- and neuropeptide-pretreated C2D ISMCs except when 10(-6) M substance P was added; IFN secretion by co-cultured T-cells was increased 4-fold under these conditions. Taken together, these data show a direct modulatory role for neuropeptides in the interaction between ISMCs and T-cells and suggest that, in general, neuropeptides may dampen immune responses in the neuromuscular layers of the inflamed intestine.
Hogaboam
C M
CM
Intestinal Disease Research Program, McMaster University, Hamilton, ON, USA. hogaboam@path.med.umich.edu
Snider
D P
DP
Collins
S M
SM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007372:Interferons / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*
D000949:Histocompatibility Antigens Class II; D009479:Neuropeptides; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007372:Interferons