Published ahead of print on September 11, 2003, doi:10.1164/rccm.200306-837OC
Am. J. Respir. Crit. Care Med., Volume 168, Number 11, December 2003, 1346-1352
A more recent version of this article appeared on December 1, 2003
Submitted on June 26, 2003
Accepted on September 9, 2003
Mycobacterium tuberculosis -specific CD8+ T cells preferentially recognize heavily infected cells
Deborah A Lewinsohn1*, Amy S Heinzel2, James M Gardner3, Liqing Zhu4, Mark R Alderson4, and David M Lewinsohn5
1 Division of Infectious Diseases and Pediatrics, Oregon Health & Science University, Portland, Oregon, USA; Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, USA; Vaccine and Gene Therapy Center, Oregon Health & Science University, Portland, Oregon, USA,
2 Division of Pulmonary and Critical Medicine and Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA; Medicine, Portland VA Medical Center, Portland, Oregon, USA,
3 Division of Infectious Diseases and Pediatrics, Oregon Health & Science University, Portland, Oregon, USA,
4 Immunology, Corixa Corporation, Seattle, Oregon, USA,
5 Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, USA; Vaccine and Gene Therapy Center, Oregon Health & Science University, Portland, Oregon, USA; Division of Pulmonary and Critical Medicine and Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA
* To whom correspondence should be addressed. 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 anti-mycobacterial 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, following recognition of antigen presenting cells displaying peptide antigen, CD4+ T cells preferentially release IFN- , 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 tuberculosisis no longer effective.
Key words: CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Cytotoxic T-Lymphocytes; Antigen Presentation
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