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The Journal of Immunology, 2005, 175: 5043-5049.
Copyright © 2005 by The American Association of Immunologists

Rapid Production of TNF-{alpha} following TCR Engagement of Naive CD8 T Cells1

Michael A. Brehm, Keith A. Daniels and Raymond M. Welsh2

Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655

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-CD3{epsilon} 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.


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