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Human Dendritic Cells Presenting Adenovirally Expressed Antigen Elicit Mycobacterium tuberculosis–Specific CD8⁺ T Cells

Division of Pediatric Infectious Diseases, Department of Molecular Microbiology and Immunology; and Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University/Portland VA Medical Center, Portland, Oregon

Correspondence and requests for reprints should be addressed to Dr. David Lewinsohn, R&D 11, Portland VA Medical Center, 3710 SW US Veterans Road, Portland, OR 97201. E-mail: lewinsod{at}ohsu.edu

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- 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.

Key Words: CD8-positive T lymphocytes • dendritic cells • tuberculosis

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