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

• Published in: Infection and Immunity 2008-05, Vol.76 (5), p.2249-2255
• Main Authors: Wu, Ying, Woodworth, Joshua S, Shin, Daniel S, Morris, Sheldon, Behar, Samuel M
• Format: Article
• Language: English
• Subjects: Animals; Applied microbiology; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacteriology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Colony Count, Microbial; Epitopes, T-Lymphocyte - immunology; Female; Fundamental and applied biological sciences. Psychology; Host Response and Inflammation; Interferon-gamma - biosynthesis; Lung - immunology; Lung - microbiology; Lymph Nodes - immunology; Mice; Mice, Inbred C3H; Microbiology; Miscellaneous; Mycobacterium bovis; Mycobacterium Infections - prevention & control; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - isolation & purification; Spleen - immunology; Spleen - microbiology; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - genetics; Vaccines, DNA - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00024-08

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-2Kk-restricted epitope CFP-10₃₂₋₃₉. These CFP-10₃₂₋₃₉-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-10₃₂₋₃₉-specific CD8⁺ T cells elicited by vaccination are sufficient to mediate protection against tuberculosis.