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Publication : Delayed clearance of filarial infection and enhanced Th1 immunity due to modulation of macrophage APC functions in xid mice.

First Author  Mukhopadhyay S Year  1999
Journal  J Immunol Volume  163
Issue  2 Pages  875-83
PubMed ID  10395682 Mgi Jnum  J:56159
Mgi Id  MGI:1340168 Doi  10.4049/jimmunol.163.2.875
Citation  Mukhopadhyay S, et al. (1999) Delayed clearance of filarial infection and enhanced Th1 immunity due to modulation of macrophage APC functions in xid mice. J Immunol 163(2):875-83
abstractText  Bruton's tyrosine kinase (Btk) mutant CBA/N mite show delayed clearance of injected microfilaria (mf) compared with Wild-type CBA/J mice. Anti-mf T cells from CBA/N mice make relatively more IFN-gamma than those from CBA/J mice. The anti-mf T cell proliferative responses are also greater in CBA/N mice. This CEA/N immune phenotype is not restricted to filarial Ags, because immunization with pure proteins also yields T cell responses of greater proliferative magnitude skewed away from Th2 cytokines in CBA/N compared with CBA/J mice. The increased magnitude of CBA/N T cell proliferative responses is reflected in increases in both precursor frequencies and clonal burst sizes of responding Ag specific T cells, and is independent of the source of re-stimulating APCs, Transfer of CBA/J peritoneal resident cells (PRCs) into CBA/N mice before pure protein immunization leads to a wild-type immune phenotype in the recipient CBA/N mice, with a reduction in the proliferative response and a relative decrease in the IFN-gamma produced. When wild-type PRC subpopulations are similarly transferred, the wild-type immune phenotype is transferred by macrophages rather than by B cells. Transfer of wild-type PRCs into CBA/N mice before injection of mf also causes similar changes in the anti-mf T cell responses and enhances the clearance of mf. Thus, Btk is involved in critical macrophage APC functions regulating priming of T cells, and can modulate these responses in pathophysiologically relevant fashion in vivo.
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