02229nas a2200313   4500000000100000008004100001260001300042653002300055653003100078653003100109653002500140653003000165653001900195653002300214653001200237653002600249653001400275653001400289653001700303653002200320100001300342700001500355700001300370245006600383300001000449490000700459520143500466022001401901       2009                            d  c2009 Sep10aBacterial Vaccines10aCD4-Positive T-Lymphocytes10aCD8-Positive T-Lymphocytes10aCell Differentiation10aCytotoxicity, Immunologic10aDrug Discovery10aImmunity, Cellular10aleprosy10aLymphocyte Activation10aTh1 Cells10aTh2 Cells10aTuberculosis10aVaccines, Subunit1 aTamura T1 aFukutomi Y1 aMakino M00a[Forefront of vaccine development: tuberculosis and leprosy].  a271-60 v783 a<p>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.</p>  a1342-3681