Rapid production of TNF-alpha following TCR engagement of naive CD8 T cells
Department of Pathology
Animals; Antigen-Presenting Cells; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Line; Cell Line, Transformed; Cell Survival; G0 Phase; Ligands; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Knockout; Receptors, Antigen, T-Cell; Tumor Necrosis Factor-alpha
Life Sciences | Medicine and Health Sciences
The acquisition of effector functions by naive CD8 T cells following TCR engagement is thought to occur sequentially with full functionality being gained only after the initiation of division. We show that naive CD8 T cells are capable of immediate effector function following TCR engagement, which stimulates the rapid production of TNF-alpha. Stimulation of splenocytes from naive mice of differing genetic backgrounds with anti-CD3epsilon mAb resulted in significant production of TNF-alpha by naive CD8 T cells within 5 h. Moreover, naive lymphocytic choriomeningitis virus-specific TCR-transgenic CD8 T cells stimulated with either their cognate peptide ligand or virus-infected cells produced TNF-alpha as early as 2 h poststimulation, with production peaking by 4 h. Naive CD8 T cells produced both membrane-bound and soluble TNF-alpha. Interfering with TNF-alpha activity during the initial encounter between naive CD8 T cells and Ag loaded dendritic cells altered the maturation profile of the APC and diminished the overall viability of the APC population. These findings suggest that production of TNF-alpha by naive CD8 T cells immediately after TCR engagement may have an unappreciated impact within the local environment where Ag presentation is occurring and potentially influence the development of immune responses.
DOI of Published Version
J Immunol. 2005 Oct 15;175(8):5043-9.
Journal of immunology (Baltimore, Md. : 1950)
Brehm, Michael A.; Daniels, Keith A.; and Welsh, Raymond M., "Rapid production of TNF-alpha following TCR engagement of naive CD8 T cells" (2005). Open Access Articles. 1094.