Delayed clearance of filarial infection and enhanced Th1 immunity due to modulation of macrophage APC functions in xid mice.
Bruton's tyrosine kinase (Btk) mutant CBA/N mice 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 CBA/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.
National Institute of Immunology, New Delhi, India.
S
S
Mukhopadhyay
P K
PK
Sahoo
A
A
George
V
V
Bal
S
S
Rath
B
B
Ravindran
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000469:parasitology; D005260:Female; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D008842:Microfilariae / Q000254:growth & development / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000276:immunology; D012719:Setariasis / Q000276:immunology* / Q000469:parasitology*; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000909:Antibodies, Helminth; C049877:maleylalbumin; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse