Human dendritic cells presenting adenovirally expressed antigen elicit Mycobacterium tuberculosis--specific CD8+ T cells.
Previous studies in murine and human models have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). Consequently, a successful tuberculosis vaccine may require the elicitation of sustained CD4+ and CD8+ T cell responses. We tested the hypothesis that the potent CD4+ T cell antigen Mtb39 is also a CD8+ T cell antigen. A recombinant adenovirus-expressing Mtb39 (adenoMtb39) was used to infect monocyte-derived dendritic cells. Using interferon-gamma enzyme-linked immunospot, Mtb39-specific CD8+ T lymphocytes were detected in three healthy individuals with latent tuberculosis infection who also had strong anti-Mtb39-specific CD4+ T cell responses. An Mtb39-specific CD8+ T cell line was generated using Mtb39-expressing dendritic cells. Mtb39-specific T cell clones were obtained by limiting dilution cloning. All seven T cell clones obtained were HLA-B44 restricted. Using a panel of synthetic overlapping peptides representative of Mtb39, the peptide epitope was identified for two clones. Furthermore, all T cell clones recognized Mtb-infected dendritic cells and were cytolytic. We conclude that infection of dendritic cells with adenoviral vectors expressing Mtb proteins allows for measurement of antigen-specific CD8+ T cell responses from peripheral blood mononuclear cells. The technique will be useful in defining CD8+ T cell antigens and in measuring immunogenicity of tuberculosis vaccines.
Lewinsohn
Deborah A
DA
Division of Pediatric Infectious Diseases, Department of Molecular Microbiology and Immunology, Oregon Health and Science University/Portland VA Medical Center, Portland, OR, USA. lewinsod@ohsu.edu
Lines
Rebecca A
RA
Lewinsohn
David M
DM
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000235:genetics; D005822:Genetic Vectors; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D000939:Epitopes; D015235:HLA-B Antigens