Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8+ T cells are sufficient to mediate protection against Mycobacterium tuberculosis infection.
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.
Wu
Ying
Y
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Building Room 516C, One Jimmy Fund Way, Boston, MA 02115, USA.
Woodworth
Joshua S
JS
Shin
Daniel S
DS
Morris
Sheldon
S
Behar
Samuel M
SM
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015169:Colony Count, Microbial; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009164:Mycobacterium Infections / Q000517:prevention & control*; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma