@article{8647, keywords = {Bacterial Vaccines, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Differentiation, Cytotoxicity, Immunologic, Drug Discovery, Immunity, Cellular, leprosy, Lymphocyte Activation, Th1 Cells, Th2 Cells, Tuberculosis, Vaccines, Subunit}, author = {Tamura T and Fukutomi Y and Makino M}, title = {[Forefront of vaccine development: tuberculosis and leprosy].}, abstract = {

The role of vaccines to tuberculosis and leprosy is to induce a cellular immunity, and as a result to induce the differentiation of memory CD8+ cytotoxic T cells. 'Help' from CD4+ T cells is important for the differentiation of naive CD8+ T cells to effector and memory CD8+ cytotoxic T cells. However, how CD4+ T cell 'help' is involved in the steps instructing T helper (Th) polarization is not yet clear. Peptide-25, a major Th epitope of Ag85B from Mycobacterium tuberculosis, preferentially induced development of Th1 cells. In contrast, altered peptide ligands (APL) that have a substitution of glycine for alanine at position 248 of Peptide-25 induced solely Th2 development. To elucidate the role of Th polarization on the 'Help' function of CD4+ T cells, we established an in vitro culture system using OVA specific CD8+ T cells, Peptide-25 specific CD4+ T cells and splenic dendritic cells (DCs). The DCs that were pre-cultured with Peptide-25 specific CD4+ T cells together with OVA and Peptide-25 induced the proliferation and granzyme B production of OVA specific CD8+ T cells. On the other hand, the DCs that were pre-cultured with Peptide-25 specific CD4+ T cells together with OVA and APL induced only proliferation of OVA specific CD8+ T cells. These results suggest that Th1 immune response induced by Peptide-25 plays an important role in the induction of functional activation of CD8+ cytotoxic T cells.

}, year = {2009}, journal = {Nihon Hansenbyo Gakkai zasshi = Japanese journal of leprosy : official organ of the Japanese Leprosy Association}, volume = {78}, pages = {271-6}, month = {2009 Sep}, issn = {1342-3681}, language = {jpn}, }