Analysis of induction and activation mechanism of protective CD8 T cells against pulmonary tuberculosis and application for the development of anti-tuberculosis vaccine

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Although importance of CD8+T cells in protection against pulmonary tuberculosis has been reported using CD8-depleted or CD8+T cell-deficient mice, it is not clear how migration and activation of the mycobacterial Ag-specific T cells are regulated in the Mycobacterium tuberculosis (Mtb)-infected lung. To address the issue, we generated pentamer of MHC H-2D^b and mycobacterial Ag Mtb32a epitope complex (D^<b->Mtb32a 5mer). Using the reagent we identified mycobacterial Mtb32a-specific CD8+T cells from day 21 in the lung and from day 28 in the mediastinal lymph node after Mtb lung infection. In contrast, Mycpbacterium bovis BCG, a vaccine strain, also express Mtb32a epitope identical to that of Mtb, and BCG subcutaneous infection induced D^b-Mtb32a 5mer-stained CD8+T cells from day 7 which is earlier than that observer after Mtb lung infection. When BCG vaccinated mice were infected with Mtb in the lung 30 days after the vaccination, induction of Mtb32a-specific CD8+T cells in the lung accelerated and clearly detected from day 7 after the infection. Furthermore, the increase of the Mtb32a-specificT cells parallel to increase of interferon-gamma production in the lung in response to Mtb32a peptide. The results suggest that induction of Mtb-specific CD8+T cells delays in the lung of Mtb-infected lung, and BCG vaccination accelerate the induction with interferon-gamma production.