The 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.