Both microbial products and T cell factors influence dendritic cell (DC) maturation. However, it is not known which T cells are capable of interacting with DCs at the initiation of adaptive immunity, when foreign antigen-specific T cells are rare. We show here that self-reactive CD1-restricted T cells can promote DC maturation by recognizing CD1 in the absence of foreign antigens. T cell recognition of all four CD1 isoforms can trigger DC maturation, but their distinct mechanisms of costimulation lead to profound differences in concomitant interleukin 12 p70 production. Distinct CD1-reactive T cells may thus differentially direct DC development early in the immune response, thereby controlling subsequent polarization of acquired immunity.

Optimum immunity against Mycobacterium tuberculosis requires both CD4 ϩ and CD8 ϩ T cells. In contrast with CD4 ϩ T cells, few antigens are known that elicit CD8 ϩ T cells during infection. CD8 ϩ T cells specific for culture filtrate protein-10 (CFP10) are found in purified protein derivative positive donors, suggesting that CFP10 primes CD8 ϩ T cells in vivo. Using T cells from M. tuberculosis -infected mice, we identified CFP10 epitopes recognized by CD8 ϩ T cells and CD4 ϩ T cells. CFP10-specific T cells were detected as early as week 3 after infection and at their peak accounted for up to 30% of CD8 ϩ T cells in the lung. IFN ␥ -producing CD8 ϩ and CD4 ϩ T cells recognizing CFP10 epitopes were preferentially recruited to the lungs of M. tuberculosis -infected mice. In vivo cytolytic activity of CD8 ϩ T cells specific for CFP10 and TB10.3/10.4 proteins was detected in the spleen, pulmonary lymph nodes, and lungs of infected mice. The cytolytic activity persisted long term and could be detected 260 d after infection. This paper highlights the cytolytic function of antigen-specific CD8 ϩ T cells elicited by M. tuberculosis infection and demonstrates that large numbers of CFP10-specific cytolytic CD8 ϩ T cells are recruited to the lung after M. tuberculosis infection.

In this study we show that like MHC class I and class II molecules, cell surface CD1d expression on APC is regulated and affects T cell activation under physiological conditions. Although IFN-γ alone is sufficient for optimum expression of MHC, CD1d requires two signals, one provided by IFN-γ and a second mediated by microbial products or by the proinflammatory cytokine TNF. IFN-γ-dependent CD1d up-regulation occurs on macrophages following infection with live bacteria or exposure to microbial products in vitro and in vivo. APC expressing higher CD1d levels more efficiently activate NKT cell hybridomas and primary NKT cells independently of whether the CD1d-restricted TCR recognizes foreign or self-lipid Ags. Our findings support a model in which CD1d induction regulates NKT cell activation.