Preapoptotic phenotype of viral epitope-specific CD8 T cells precludes memory development and is an intrinsic property of the epitope
UMass Chan Affiliations
Department of PathologyProgram in Immunology and Virology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2004-10-08Keywords
Animals; Annexin A5; Antigens, CD3; Antigens, Viral; *Apoptosis; CD8-Positive T-Lymphocytes; DNA Fragmentation; *Epitopes, T-Lymphocyte; Glycoproteins; *Immunologic Memory; Immunophenotyping; Interferon Type II; Interleukin-2; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred C57BL; Nucleocapsid Proteins; Nucleoproteins; Organ Specificity; Peptide Fragments; Receptors, Interleukin-7; Viral Core Proteins; Viral ProteinsLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Virus-specific CD8 T cells after clearance of infection reduce their number in lymphoid organs by apoptotic death and by migration into peripheral tissues. During and after infection, many lymphocytic choriomeningitis virus (LCMV)-specific CD8 T cells in lymphoid but not peripheral tissues are in a preapoptotic state, as detected by the early apoptosis marker annexin V. In this report, we investigated the significance of this preapoptotic state and how it may be influenced by viral epitope specificity. Stimulation with anti-CD3 or IL-2 in vitro postponed DNA fragmentation in annexin V+ cells, but adoptive transfer studies in vivo showed that this preapoptotic phenotype precluded the development of functional memory. CD8 T cells specific to LCMV epitopes NP396 and gp33 differed in their preapoptotic state, with NP396-specific T cells binding more annexin V than gp33-specific T cells. These epitope- and tissue-dependent differences were seen in primary, memory, and secondary responses and in mice receiving different displays of Ag by infection with LCMV strains of different tropisms or by infection with vaccinia virus recombinants expressing LCMV proteins. Thus, the epitope-dependent differences in apoptosis were independent of virus tropisms, duration of Ag exposure, and competition within APCs, and were an intrinsic property of the epitope. The tissue-dependent and epitope-dependent preapoptotic state correlated with reduced expression of IL-7Ralpha.Source
J Immunol. 2004 Oct 15;173(8):5138-47.
DOI
10.4049/jimmunol.173.8.5138Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32772PubMed ID
15470058Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.173.8.5138