Cloning of TH0- and TH2-type helper lymphocytes from liver granulomas of Schistosoma mansoni-infected mice.
The pathological manifestations of schistosomiasis mansoni are primarily induced by circumovum hepatic granuloma formation and fibrosis. The growth and modulation of the granulomas are regulated by T lymphocytes and their products. In the present study, we isolated T-lymphocyte clones from lesions at the acute and chronic stages of murine infection. All of the T-cell clones were characterized by immunofluorescence as CD4+CD8- helper cells. Three T-cell clones derived from vigorous granulomas produced interleukin 2 (IL-2), IL-4, and gamma interferon (IFN-gamma) and were therefore classified as TH0-type T lymphocytes. Of the three clones derived from immunomodulated lesions, two produced IL-2 or IL-4 and/or IFN-gamma (TH0 type) and the other one did not produce IFN-gamma but did produce IL-4 and was therefore characterized as a TH2-type helper clone. The clones were further characterized by their responsiveness to soluble egg antigen fractions. The acute infection-derived clones responded to the lower-molecular-mass (60- to 66-kDa and 25- to 30-kDa) fractions, whereas the immunomodulated-granuloma-derived clones responded to the 60- to 66-kDa and higher-molecular-mass (70- to 90-, 93- to 125-, and > 200-kDa) fractions. Upon adoptive transfer into naive mice, both the TH0- and TH2-type clones were capable of inducing granuloma formation of similar magnitude around antigen-coated beads and/or freshly isolated parasite eggs. The present study revealed the presence of TH0-type precursor helper cells within the liver granulomas. The findings underscore the complexity of the granulomatous response at the T-cell level and demonstrate that both TH0- and TH2-type granuloma lymphocytes play a role in parasite egg-induced granuloma formation.
Zhu
Y
Y
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Lukacs
N W
NW
Boros
D L
DL
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002999:Clone Cells; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000276:immunology*; D008109:Liver Diseases, Parasitic / Q000276:immunology*; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008808:Mice, Inbred CBA; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D000947:Antigens, Helminth; D008222:Lymphokines