In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 8 ( 2000-04-11), p. 4204-4208
Abstract:
A necessary role for cytotoxic T lymphocytes in protection against Mycobacterium tuberculosis (MTB) has been suggested by studies of the β2-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 β2-microglobulin −/− , followed by transporter associated with antigen processing deficient (TAP1 −/− ), CD8α −/− , 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 ) β2-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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.97.8.4204
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Bookmarklink