CD4+ T cells contain Mycobacterium tuberculosis infection in the absence of CD8+ T cells in mice vaccinated with DNA encoding Ag85A.
The contribution of CD8+ and CD4+ T cell-mediated effector functions against Mycobacterium tuberculosis infection elicited by i.m. vaccination with plasmid DNA encoding the immunodominant Ag85A antigen of M. tuberculosis was studied. Ag85A DNA-vaccinated beta2-microglobulin gene-deficient (beta2m-/-) mice, which lack CD8+ T cells, produced Ag85-specific antibodies and Th1 type cytokines similar to wild-type mice. Although beta2m-/- mice were more susceptible to M. tuberculosis infection, following vaccination they efficiently controlled bacterial replication in spleen and lungs 4 weeks post-infection. In contrast, mice lacking CD4+ T cells were neither sensitized by the Ag85A DNA vaccine to produce Ag85-specific antibodies or Th1 type cytokines nor did they contain a M. tuberculosis challenge infection. In addition, Ag85A DNA-vaccinated IFN-gamma gene knockout mice produced Ag85-specific antibodies and IL-2 but died rapidly following a M. tuberculosis challenge infection. Collectively, these data support the view that IFN-gamma-producing CD4+ T cells, independently of CD8+ T cells, may mediate the protective effect of the Ag85A DNA vaccine.
D'Souza
S
S
The Laboratory of Mycobacterial Immunology, Pasteur Institute of Brussels, Belgium. sdsouza@ben.vub.ac.be
Denis
O
O
Scorza
T
T
Nzabintwali
F
F
Verschueren
H
H
Huygen
K
K
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000502:physiology
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D019444:Vaccines, DNA; C065036:antigen 85, Mycobacterium bovis; D001613:beta 2-Microglobulin; D007371:Interferon-gamma