Rapid production of TNF-alpha following TCR engagement of naive CD8 T cells.
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.
Brehm
Michael A
MA
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Daniels
Keith A
KA
Welsh
Raymond M
RM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha