The Journal of Experimental Medicine
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Published online 5 February 2001.
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© The Rockefeller University Press, 0022-1007/2001/2/271/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 3, February 5, 2001 271-280


Original Article

The Relative Importance of T Cell Subsets in Immunity and Immunopathology of Airborne Mycobacterium tuberculosis Infection in Mice

Tirsit Moguesa, Mariam E. Goodricha, Lynn Ryana, Ronald LaCoursea, and Robert J. Northa

a The Trudeau Institute, Saranac Lake, New York 12983
The Trudeau Institute, 100 Algonquin Ave., Saranac Lake, NY 12983.518-891-5126518-891-3080

rjnorth{at}northnet.org

Wild-type (WT) and targeted-mutant mice incapable of making {alpha}β T cells, {gamma}{delta} T cells, class I major histocompatibility complex (MHC), class II MHC, interferon (IFN)-{gamma}, or inducible nitric oxide synthase (NOS2), were infected with Mycobacterium tuberculosis (Mtb) by aerosol, and monitored over time for their ability to (a) control infection, (b) develop histopathology 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 alveolitis at sites of infection, with increased synthesis of IFN-{gamma} and NOS2 mRNA, and with an median survival time (MST) of 258.5 d. In the absence of {alpha}β T cells, Mtb grew progressively and rapidly to induce a necrotic, 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–mediated immunity, lung infection was controlled at a 1 log higher stationary level that induced a similar histopathologic response to that of WT mice, and resulted in an MST of 232 d.

Key Words: {alpha}β • CD8 • CD4 • interferon {gamma} • nitric oxide synthase


Abbreviations used in this paper: MST, median survival time; Mtb, Mycobacterium tuberculosis; NOS2, inducible nitric oxide synthase; RPA, ribonuclease protection assay; WT, wild-type.

© 2001 The Rockefeller University Press


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