Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 97, Issue 8, Pages 4204-4208Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.97.8.4204
Keywords
CD8(+) T cells; perforin; beta 2-microglobulin; transporter associated with antigen processing; CD1d
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Funding
- NIAID NIH HHS [R01 AI007118, AI 07118, AI 23545] Funding Source: Medline
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A necessary role for cytotoxic T lymphocytes in protection against Mycobacterium tuberculosis (MTB) has been suggested by studies of the beta 2-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 beta 2-microglobulin(-/-), followed by transporter associated with antigen processing deficient (TAP1(-/-)), CD8 alpha(-/-), 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) beta 2-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.
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