Contribution of Th1 and Th2 cells to protection and pathology in experimental models of granulomatous lung disease.
Mice that had received adoptive transfer of DO11.10 TCR transgenic T cells polarized toward a Th1 or a Th2 phenotype were challenged with Ag-coated beads or with recombinant Mycobacterium tuberculosis expressing the OVA determinant. The resulting bead-induced pulmonary granulomas reflected the phenotype of the adoptively transferred T cells, with the Th2 cells promoting a fibrotic reaction. Mice receiving Th1 cells mounted an epitope-specific protective response to challenge with recombinant M. tuberculosis. Th2 recipients were characterized by enhanced weight loss and lung fibrosis during acute high-dose infection. The combination of TCR transgenic T cells and epitope-tagged mycobacteria provides a novel experimental model for investigation of the pathogenesis of tuberculosis.
Wangoo
A
A
Department of Respiratory Medicine, National Heart and Lung Institute, London, United Kingdom.
Sparer
T
T
Brown
I N
IN
Snewin
V A
VA
Janssen
R
R
Thole
J
J
Cook
H T
HT
Shaw
R J
RJ
Young
D B
DB
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000209:etiology / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D007275:Injections, Intravenous; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014376:Tuberculosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control
D000941:Antigens; D016207:Cytokines; D010047:Ovalbumin