Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice.

Sousa AO, Mazzaccaro RJ, Russell RG, Lee FK, Turner OC, Hong S, Van Kaer L, Bloom BR
Proc Natl Acad Sci U S A. 2000 97 (8): 4204-8

PMID: 10760288 · PMCID: PMC18197 · DOI:10.1073/pnas.97.8.4204

A necessary role for cytotoxic T lymphocytes in protection against Mycobacterium tuberculosis (MTB) has been suggested by studies of the beta2-microglobulin-deficient mouse, which is unable to present antigens through MHC class I and class I-like molecules and invariably succumbs early after infection. To identify the relative contributions of distinct putative MHC class I-dependent cell populations in protection against tuberculosis, we compared a variety of gene-disrupted mouse strains for susceptibility to MTB infection. Among the strains tested, the most susceptible mice, as measured by survival time and bacterial loads, were the beta2-microglobulin(-/-), followed by transporter associated with antigen processing deficient (TAP1(-/-)), CD8alpha(-/-), perforin(-/-), and CD1d(-/-) mice. These findings indicated that (i) CD8(+) T cells contribute to protection against MTB, and their protective activity is only partially dependent on perforin; (ii) beta2-microglobulin-dependent T cell populations distinct from CD8(+) T cells also contribute to anti-MTB immunity; and (iii) protective immune mechanisms are predominantly TAP-dependent, although TAP-independent mechanisms also contribute to protection. Because CD1d-deficient animals were fully resistant to MTB, other TAP-independent mechanisms must contribute to protection. We suggest here that both classical and nonclassical MHC class I-restricted T cells, distinct from CD1d-restricted cells, may be involved in protective immune responses against tuberculosis.

MeSH Terms (8)

Animals CD8-Positive T-Lymphocytes Histocompatibility Antigens Class I Lung Mice Mice, Inbred C57BL Mice, Knockout Tuberculosis

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