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Mycobacterium tuberculosis–specific CD8⁺ T Cells Preferentially Recognize Heavily Infected Cells

Division of Infectious Diseases, Department of Pediatrics, Department of Molecular Microbiology and Immunology, Vaccine and Gene Therapy Center, and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University; and Portland Veterans Affairs Medical Center, Portland, Oregon; and Corixa Corporation, Seattle, Washington

Correspondence and requests for reprints should be addressed to Deborah Lewinsohn, M.D., Department of Pediatrics, Oregon Health and Science University, 707 S.W. Gaines Road, CDRCP, Portland, OR 97239. E-mail: lewinsde{at}OHSU.edu

Both CD4⁺ and CD8⁺ T cells are important for successful immunity to tuberculosis and have redundant effector functions, such as cytolysis and release of potent antimycobacterial cytokines such as interferon- and tumor necrosis factor-. We hypothesized that CD8⁺ T cells play a unique role in host defense to Mycobacterium tuberculosis infection as well. Possibilities include preferential and/or enhanced release of granular constituents and/or preferential recognition of heavily infected cells. Utilizing human, Mycobacterium tuberculosis–specific, CD4⁺ and CD8⁺ T cell clones, we demonstrate that, after recognition of antigen-presenting cells displaying peptide antigen, CD4⁺ T cells preferentially release interferon-, whereas CD8⁺ T cells preferentially lyse antigen-presenting cells. Furthermore, utilizing dendritic cells infected with Mycobacterium tuberculosis expressing green fluorescent protein, we show that CD8⁺ T cells preferentially recognize heavily infected cells that constitute the minority of infected cells. These data support the hypothesis that the central role of CD8⁺ T cells in the control of infection with Mycobacterium tuberculosis may be that of surveillance; in essence, recognition of cells in which the containment of Mycobacterium tuberculosis is no longer effective.

Key Words: antigen presentation • CD4-positive T lymphocytes • CD8-positive T lymphocytes • cytotoxic T lymphocytes

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