The Xid defect determines an improved clinical course of murine leishmaniasis in susceptible mice.
The course of Leishmania major infection in B cell-defective BALB.Xid mice was investigated. Infected BALB.Xid mice showed a significantly slower lesion development compared with BALB/c controls accompanied by a 10- to 30-fold lower parasite burden in lymphatic organs. The B cell immune response, as quantified by anti-leishmanial antibody production and B cell numbers in lymphatic organs, remained significantly lower in BALB.Xid mice as compared with BALB/c control mice. In accordance with disease development, CD4+ T cells from lymph nodes of infected BALB.Xid mice produced 6- to 10-fold more IFN-gamma than the respective T cells of BALB/c mice, when stimulated with leishmanial antigen in vitro. B cells from lymph nodes and the peritoneal cavities of BALB/c mice could be induced to produce 3- to 8-fold more IL-10 than the respective cells from B cell-defective BALB.Xid mice. The data thus indicate that the Xid mutation allows for the development of Th1 cells which confer resistance to infection with L. major. Moreover, the data suggest that B cells contribute to susceptibility to L. major infection in BALB/c mice by skewing the Th cell network towards a Th2 phenotype. Since the difference in B cell-derived IL-10 production between BALB/c and BALB.Xid mice was more prominent in peritoneal B cells, the data support the notion that the skewing of the T cell response may be predominantly mediated by the B1 cell subset.
Hoerauf
A
A
Institute of Clinical Microbiology, University of Erlangen-Nürnberg, Germany.
Solbach
W
W
Lohoff
M
M
Röllinghoff
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D007136:Immunoglobulins; D016753:Interleukin-10; D007371:Interferon-gamma