T cells and cytokines in intracellular bacterial infections: experiences with Mycobacterium bovis BCG.
Intracellular bacteria reside in mononuclear phagocytes, and protective immunity is dominated by T lymphocytes. Mycobacterium bovis bacillus Calmette-Guéin (BCG) infection of mice represents an excellent model for studying immune mechanisms involved in defence against persistent intracellular bacteria that cause chronic disease. Gene disruption mutant mice include: A beta-/-, which lack conventional CD4+ T cell receptor alpha/beta (TCR alpha/beta) T lymphocytes; beta 2 microglobulin -/-, which lack conventional CD8+ TCR alpha/beta lymphocytes; TCR beta-/-, which lack all TCR alpha/beta lymphocytes; TCR delta-/-, which lack all TCR gamma/delta lymphocytes; and RAG-1-/- mutants, which lack mature T and B lymphocytes. Studies of these mutants suggest that CD4+ TCR alpha/beta, CD8+ TCR alpha/beta and TCR gamma/delta T lymphocytes all contribute to immunity against M. bovis BCG. Activation of antibacterial effector functions in macrophages by T helper 1 (Th1) cell-derived gamma-interferon (IFN-gamma) is central to protection. In contrast, Th2 cells are only marginally involved. Activation of Th1 and Th2 cells is regulated by interleukin 10 (IL-10) and IL-12, which are induced early in infection with M. bovis BCG. Although IL-12 is stimulated by M. bovis BCG in immunocompetent mice, studies with IFN-gamma receptor-deficient and tumour necrosis factor alpha (TNF-alpha) receptor-deficient mutant mice suggest that M. bovis BCG-induced IL-12 secretion depends on IFN-gamma and TNF-alpha. Hence, IL-12 cannot be the first cytokine produced during M. bovis BCG infection.
Kaufmann
S H
SH
Department of Immunology, University of Ulm, Germany.
Ladel
C H
CH
Flesch
I E
IE
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D009163:Mycobacterium bovis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology
D016207:Cytokines