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

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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.