T Cells and Cytokines in Intracellular Bacterial Infections: Experiences with Mycobacterium Bovis BCG

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Abstract
Intracellular bacteria reside in mononuclear phagocytes, and protective immunity is dominated by T lymphocytes. Mycobacterium bovis bacillus Calmette‐Guérin (BCG) infection of mice represents an excellent model for studying immune mechanisms involved in defence against persistent intra‐cellular bacteria that cause chronic disease. Gene disruption mutant mice include: Aβ−/−, which lack conventional CD4+ T cell receptor α/β (TCRα/β) T lymphocytes; β2 microglobulin−/−, which lack conventional CD8+ TCRα/β lymphocytes; TCRβ−/−, which lack all TCRα/β lymphocytes; TCRδ−/−, which lack all TCRγ/δ lymphocytes; and RAG‐1−/− mutants, which lack mature T and B lymphocytes. Studies of these mutants suggest that CD4+ TCRα/β, CD8+ TCRα/β and TCRγ/δ T lymphocytes all contribute to immunity against M . bovis BCG. Activation of antibacterial effector functions in macrophages by T helper 1 (Thl) cell‐derived γ‐interferon (IFN‐γ) is central to protection. In contrast, Th2 cells are only marginally involved. Activation of Thl 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‐γ receptor‐deficient and tumour necrosis factor α (TNF‐α) receptor‐deficient mutant mice suggest that M. bovis BCG‐induced IL‐12 secretion depends on IFN‐γ and TNF‐α. Hence, IL‐12 cannot be the first cytokine produced during M. bovis BCG infection.