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 Mycobact erium tuberculosis (MTB) has been suggested by studies of the beta 2-microg lobulin-deficient mouse, which is unable to present antigens through MHC cl ass I and class I-like molecules and invariably succumbs early after infect ion. To identify the relative contributions of distinct putative MHC class I-dependent cell populations in protection against tuberculosis, we compare d a variety of gene-disrupted mouse strains for susceptibility to MTB infec tion. Among the strains tested, the most susceptible mice, as measured by s urvival time and bacterial loads, were the beta 2-microglobulin(-/-), follo wed by transporter associated with antigen processing deficient (TAP1(-/-)) , CD8 alpha(-/-), perforin(-/-), and CD1d(-/-) mice. These findings indicat ed that (i) CD8(+) T cells contribute to protection against MTB, and their protective activity is only partially dependent on perforin; (ii) beta 2-mi croglobulin-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 cont ribute to protection. Because CD1d-deficient animals were fully resistant t o MTB, other TAP-independent mechanisms must contribute to protection. We s uggest here that both classical and nonclassical MHC class I-restricted T c ells, distinct from CD1d-restricted cells, may be involved in protective im mune responses against tuberculosis.