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Contribution of Th1 and Th2 Cells to Protection and Pathology in Experimental Models of Granulomatous Lung Disease¹

Arun Wangoo^*, Tim Sparer^*, Ivor N. Brown, Valerie A. Snewin, Riny Janssen, Jelle Thole, H. Terence Cook, Rory J. Shaw^* and Douglas B. Young^2,

^* Department of Respiratory Medicine, National Heart and Lung Institute, and Departments of Infectious Diseases and Microbiology and Histopathology, Imperial College School of Medicine, London, United Kingdom

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.

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