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 s lower 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 productio n 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 respectiv e 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 resp ective cells from B cell-defective BALB.Xid mice. The data thus indica te that the Xid mutation allows for the development of T(h)1 cells whi ch confer resistance to infection with L. major. Moreover, the data su ggest that B cells contribute to susceptibility to L. major infection in BALB/c mice by skewing the T-h cell network towards a T(h)2 phenoty pe. Since the difference in B cell-derived IL-10 production between BA LB/c and BALB.Xid mice was more prominent in peritoneal B cells, the d ata support the notion that the skewing of the T cell response may be predominantly mediated by the B1 cell subset.