期刊
JOURNAL OF IMMUNOLOGY
卷 175, 期 8, 页码 5043-5049出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.8.5043
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资金
- NIAID NIH HHS [AI-17672, AI-42669, AI-46629] Funding Source: Medline
- NIAMS NIH HHS [AR-35506] Funding Source: Medline
- NIDDK NIH HHS [DK52530] Funding Source: Medline
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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