title: Th1-polarizing immunization with egg antigens correlates with severe exacerbation of immunopathology and death in schistosome infection.
abstract: In schistosomiasis mansoni, parasite eggs precipitate an intrahepatic granulomatous and fibrosing inflammatory process, which is mediated by, and dependent on, MHC class II-restricted CD4 T helper (Th) lymphocytes specific for schistosome egg antigens (SEA). In the mouse model of the disease, CBA mice develop large granulomas, whereas in C57BL/6 (BL/6) mice these granulomas are significantly smaller. To further investigate how the prevailing cytokine environment influences the development of the egg-induced immunopathology, we immunized the low-pathology BL/6 mice with SEA in complete Freund's adjuvant (CFA) once before, and once again during, the course of a 7-week infection. This immunization caused a pronounced Th1 shift in the SEA-specific CD4 T cell response, which was detected in the mesenteric lymph nodes (MLNs) and spleens, as well as in the granulomatous lesions themselves. The immunized mice displayed a dramatic enhancement of hepatic egg-induced immunopathology manifested by a marked increase in granuloma size and parenchymal inflammation, leading to early death. Control mice immunized with equivalent amounts of SEA or CFA alone displayed the smaller hepatic lesions in a Th2-dominant environment typically seen in the unimmunized BL/6 mice. Analysis of granuloma and MLN lymphocytes from the SEA/CFA-immunized mice revealed that the proportion of CD4 T cells was unchanged in comparison with the control BL/6 groups and remained significantly lower than that seen in the normally high-pathology CBA strain. These results suggest that the shift toward Th1-type cytokine production by a numerically stable population of CD4 T cells correlates with severe exacerbation of immunopathology in schistosomiasis.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: L I
authors.initials: LI
authors.lastname: Rutitzky
authors.forename: H J
authors.initials: HJ
authors.lastname: Hernandez
authors.forename: M J
authors.initials: MJ
authors.lastname: Stadecker
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010063:Ovum / Q000276:immunology; D012552:Schistosomiasis / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan