Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice.
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.
Sousa
A O
AO
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Mazzaccaro
R J
RJ
Russell
R G
RG
Lee
F K
FK
Turner
O C
OC
Hong
S
S
Van Kaer
L
L
Bloom
B R
BR
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control* / Q000662:veterinary
D015395:Histocompatibility Antigens Class I