Production of a fibroblast-stimulating factor by Schistosoma mansoni antigen-reactive T cell clones.
Fibrosis in schistosomiasis is the terminal event of a complex pathophysiologic cascade involving interactions between fibroblasts and both host and parasite products. In the present study, the effect of lymphokines produced by cloned Schistosoma mansoni antigen-reactive T cells on the proliferation of murine fibroblasts was investigated. These T cells previously have been shown to proliferate, produce lymphokines, mediate delayed-type hypersensitivity responses, and generate in vitro granulomas in response to soluble egg antigen (SEA). T cells, co-cultured with irradiated antigen-presenting cells and pulsed with SEA, produced levels of fibroblast-stimulating factor (FSF) comparable to equivalent numbers of dispersed hepatic granuloma cells isolated from infected mice. Supernatants of cloned T cells pulsed with Con A (in the absence of macrophages) contained no detectable interleukin 1 activity, but did stimulate fibroblast activation and growth. T cell FSF activity was trypsin-sensitive, was stable at 56 degrees C but not to boiling, and was retained by Con A Sepharose. Activity was associated with HPLC fractions corresponding to an m.w. of 10,000 to 40,000. Neither recombinant interferon-gamma nor affinity-purified interleukin 2 was capable of stimulating fibroblast proliferation. In functional studies, the degree of fibroblast proliferation was related to the length of exposure to the factor. In addition, quiescent fibroblasts were maximally stimulated by T cell FSF only if a second co-factor such as insulin or epidermal growth factor was present. The synergism between T cell FSF and known progression factors suggests that FSF-T may provide a competence signal to fibroblasts. The present results suggest that a direct molecular link may exist between T cells and fibroblasts in schistosomiasis.
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002455:Cell Division; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051381:Rats; D011917:Rats, Inbred Lew; D012550:Schistosoma mansoni / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D000947:Antigens, Helminth; D007328:Insulin; D005346:Fibroblast Growth Factors; D013936:Thymidine