The relative importance of T cell subsets in immunity and immunopathology of Airborne Mycobacterium tuberculosis infection in mice

Wild-type (WT) and targeted-mutant mice incapable of making alpha beta T ce lls, gamma delta T cells, class I major histocompatibility complex (MHC), c lass II MHC, interferon (IFN)-gamma, or inducible nitric oxide synthase (NO S2), were infected with Mycobacterium tuberculosis (Mtb) by aerosol, and mo nitored over time for their ability to (a) control infection, (b) develop h istopathology at sites of infection, and (c) survive. WT mice acquired the ability to control and to hold infection at a stationary level from day 20 on. This was associated with the development of a macrophage-dominated alve olitis at sites of infection, with increased synthesis of IFN-gamma and NOS 2 mRNA. and with an median survival time (MST) of 258.5 d. In the absence o f alpha beta T cells, Mtb grew progressively and rapidly to induce a necrot ic, neutrophil-dominated lung pathology that killed mice with an MST of 48 d. In the absence of CD4-mediated immunity (class II-/- mice), progressive bacterial growth continued in the lungs and in other organs beyond day 20, resulting in an MST of 77 d. By contrast, in the absence of CD8 T cell-medi ated immunity, lung infection was controlled at a 1 log higher stationary l evel that induced a similar histopathologic response to that of WT mice, an d resulted in an MST of 232 d.