Th1-polarizing immunization with egg antigens correlates with severe exacerbation of immunopathology and death in schistosome infection

In schistosomiasis mansoni, parasite eggs precipitate an intrahepatic granu lomatous and fibrosing inflammatory process, which is mediated by, and depe ndent on, MHC class II-restricted CD4 T helper (Th) lymphocytes specific fo r schistosome egg antigens (SEA). In the mouse model of the disease, CBA mi ce develop large granulomas, whereas in C57BL/6 (BL/6) mice these granuloma s are significantly smaller. To further investigate how the prevailing cyto kine environment influences the development of the egg-induced immunopathol ogy, 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 Thl shift in the SEA-speci fic 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 immu nopathology manifested by a marked increase in granuloma size and parenchym al inflammation, leading to early death. Control mice immunized with equiva lent amounts of SEA or CFA alone displayed the smaller hepatic lesions in a Th2-dominant environment typically seen in the unimmunized BL/6 mice. Anal ysis of granuloma and MLN lymphocytes from the SEA/CFA-immunized mice revea led 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 t oward Th1-type cytokine production by a numerically stable population of CD 4 T cells correlates with severe exacerbation of immunopathology in schisto somiasis.