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

Content Provider	PubMed Central
Author	Rutitzky, Laura I. Hernandez, Hector J. Stadecker, Miguel J.
Copyright Year	2001
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.
Related Links	http://dx.doi.org/10.1073/pnas.231258498
Ending Page	13248
Page Count	6
Starting Page	13243
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	98
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2001-11-06
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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