Functions and specificity of T cells following nucleic acid vaccination of mice against Mycobacterium tuberculosis infection.
The 38-kDa glycolipoprotein of Mycobacterium tuberculosis has been known to evoke prominent T cell and Ab responses in patients with active tuberculosis. In this study, we investigated its protective capacity using plasmid DNA immunization in a mouse experimental model. Prior knowledge of several antigenic determinants has been beneficial for analyzing the phenotype and specificity of T cells, which determine the efficacy of this vaccination procedure. C57BL/6 mice responded to the 38-kDa gene-pcDNA3 plasmid with strong CD4+ Th1 and CD8+ cytotoxic T cell responses of the IFN-gamma-producing Tc1 phenotype. After challenge with virulent tubercle bacilli, the bacterial load in the spleens and lungs of vaccinated mice was reduced to a level similar to that imparted by Mycobacterium bovis Bacille Calmette-Guérin vaccination. Notably, the specificity of CD4+ and CD8+ T cells from DNA-vaccinated and tubercle-infected mice was found to be strikingly different in respect of several peptide epitopes. The identified peptides recognized by T cells from protected mice are of further interest for the development of subunit-based vaccines against tuberculosis.
Zhu
X
X
Medical Research Council Clinical Sciences Centre, Tuberculosis & Related Infections Unit, Hammersmith Hospital, London, United Kingdom.
Venkataprasad
N
N
Thangaraj
H S
HS
Hill
M
M
Singh
M
M
Ivanyi
J
J
Vordermeier
H M
HM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004269:DNA, Bacterial / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010957:Plasmids / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D014611:Vaccination
D004269:DNA, Bacterial; D000939:Epitopes; D007371:Interferon-gamma