Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice
Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice
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DOI：
10.1073/pnas.97.8.4204
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Bloom, BR
中科院分区：
文献类型：
--
作者：
Sousa, AO;Mazzaccaro, RJ;Bloom, BR
对β 2-微球蛋白缺陷小鼠的研究表明，细胞毒性T淋巴细胞在预防结核分枝杆菌（MTB）中具有必要的作用，β 2-微球蛋白缺陷小鼠不能通过MHC I类和I类分子呈递抗原，并且在感染后早期总是死亡。为了确定不同的推定的MHC I类依赖性细胞群体在预防结核病方面的相对贡献，我们比较了多种基因破坏的小鼠品系对MTB感染的易感性。在测试的菌株中，根据存活时间和细菌载量测量，最易感的小鼠是β 2-微球蛋白（-/-），其次是抗原加工缺陷相关转运蛋白（TAP 1（-/-））、CD 8 α（-/-）、穿孔素（-/-）和CD 1d（-/-）小鼠。这些发现表明：（i）CD 8（+）T细胞有助于防止MTB，其保护活性仅部分依赖于穿孔素;（ii）与CD 8（+）T细胞不同的β 2-微球蛋白依赖性T细胞群也有助于抗MTB免疫;（iii）保护性免疫机制主要是TAP依赖性的，尽管TAP非依赖性机制也有助于保护。由于CD 1d缺陷动物对MTB具有完全抵抗力，因此其他独立于TAP的机制必须有助于保护。我们在这里建议，经典和非经典的MHC I类限制性T细胞，不同的CD 1d限制性细胞，可能参与对结核病的保护性免疫反应。
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.