Vaccine-Elicited 10-Kilodalton Culture Filtrate Protein-Specific CD8 + T Cells Are Sufficient To Mediate Protection against Mycobacterium tuberculosis Infection

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Abstract
The 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secretory antigen of T cells (ESAT-6) are secreted in abundance by Mycobacterium tuberculosis and are frequently recognized by T cells from infected people. The genes encoding these proteins have been deleted from the genome of the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin (BCG), and it is hypothesized that these proteins are important targets of protective immunity. Indeed, vaccination with ESAT-6 elicits protective CD4 + T cells in C57BL/6 mice. We have previously shown that M. tuberculosis infection of C3H mice elicits CFP-10-specific CD8 + and CD4 + T cells. Here we demonstrate that immunization with a CFP-10 DNA vaccine stimulates a specific T-cell response only to the H-2K k -restricted epitope CFP-10 32-39 . These CFP-10 32-39 -specific CD8 + cells undergo a rapid expansion and accumulate in the lung following challenge of immunized mice with aerosolized M. tuberculosis . Protective immunity is induced by CFP-10 DNA vaccination as measured by a CFU reduction in the lung and spleen 4 and 8 weeks after challenge with M. tuberculosis . These data demonstrate that CFP-10 is a protective antigen and that CFP-10 32-39 -specific CD8 + T cells elicited by vaccination are sufficient to mediate protection against tuberculosis.

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