Dendritic cells pulsed with either secretory antigens of Mycobacterium tuberculosis or live mycobacteria show a differential expansion of Th1, Th2 and Th3 type T cells in immune mice (92.10)

Abstract

Dendritic cells (DCs) can prime naïve or immune T cells and expand Th1, Th2 and Th3 type of T cells that determine protection against pathogens. While the Th1 immunity has been thought to be protective against tuberculosis, the ability of vaccines to induce Th1-Th3 immunity is unclear. Emerging tuberculosis vaccines include DNA vaccines encoding 85 complex (A, B, C), ESAT-6 and CFP-10 (ES antigens) or live attenuated Mycobacterium tuberculosis (MTB) in comparison with BCG vaccine. Interestingly, MTB H37Rv secretes all three ES antigens while BCG secretes Ag85 but lacks ESAT-6 and CFP-10. We therefore hypothesized that ES antigens and live bacteria may induce different types of T cell responses and the efficacy of vaccines delivering these would vary in mice. METHODS: Bone marrow derived C57Bl/6 DCs were infected with live H37Rv or BCG or were pulsed with Ag85(ABC), ESAT-6 or CFP-10 antigens. After 24 h, they were cocultured with naïve T cells or immune T cells from heat killed MTB immunized mice. T cells were then stained for intracellular T-bet/IFN-γ, GATA3/IL-4 and Foxp3/IL-10 to determine the expansion of Th1, Th2 and Th3 response respectively. RESULTS: ES antigens induced a strong Th1 response with very little Th2 or Th3 responses in immune T cells. Paradoxically, H37Rv and BCG induced a Th1 response as well as significant levels of Th2 and Th3 type of T cells. CONCLUSIONS: We suggest that live mycobacterial vaccines concurrently induce deleterious Th2 and Th3 T cells during vaccination or infection that may affect the protective function of Th1 T cells.