[Forefront of vaccine development: tuberculosis and leprosy].
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.
Tamura
Toshiki
T
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan. toshikit@nih.go.jp
Fukutomi
Yasuo
Y
Makino
Masahiko
M
D001428:Bacterial Vaccines; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D055808:Drug Discovery; D007111:Immunity, Cellular; D007918:Leprosy / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D022223:Vaccines, Subunit
D001428:Bacterial Vaccines; D022223:Vaccines, Subunit; C060596:anti-leprosy vaccine