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.
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.