New anti-tuberculosis vaccine strategies by the use of the CD1-lipid antigen presentation pathway

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Despite the extensive use of BCG as an anti-tuberculosis vaccine, its ability to induce CD1-dependent, lipid-specific immune responses has not been examined. In guinea pigs vaccinated with BCG, splenic T cells responded by proliferation to mycobacteria-derived protein antigens, but not to lipid antigens. However, in cytolytic assays using guinea pig CD1-transfected fibroblasts as target cells, splenic T cells were able to recognize and kill BCG lipid-pulsed, but not unpulsed, target cells that express either CD1b2,CD1b3, or CD1b4 isoforms. Thus, live BCG vaccination resulted in activation of cytotoxic T cells that specifically recognize BCG-derived lipids in a CD1-dependent manner, which was parallel to our previous identification of CD8-positive, CD1-restricted T cells in the circulation of BCG-vaccinated human individuals. These results demonstrated an outstanding ability of BCG to induce lipid-specific T cell responses that had never been appreciated previously.In addition to the cell-mediated immunity, IgG antibody responses to mycobacteria-derived lipids, including an essential cell wall glycolipid, lipoarabinomannan, were detected in BCG-vaccinated guinea pigs. Given that lipoarabinomannan suppresses several aspects of host immunity, allowing the bacteria to survive in the host, production of specific antibodies may contribute to protection against mycobacterial infection. Taken together, results obtained from this study underscore a role for the lipid-specific acquired immunity in host defense against tuberculosis, and thus, raise the important possibility for a new type of lipid-based anti-tuberculosis vaccines.