CD4+ T cells contain Mycobacterium tuberculosis infection in the absence of CD8+ T cells in mice vaccinated with DNA encoding Ag85A

Eur J Immunol. 2000 Sep;30(9):2455-9. doi: 10.1002/1521-4141(200009)30:9<2455::AID-IMMU2455>3.0.CO;2-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • BCG Vaccine / immunology*
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Vaccination
  • Vaccines, DNA / immunology*
  • beta 2-Microglobulin / physiology

Substances

  • Antigens, Bacterial
  • BCG Vaccine
  • Vaccines, DNA
  • antigen 85, Mycobacterium bovis
  • beta 2-Microglobulin
  • Interferon-gamma