GSBS Student Publications

Title

Preapoptotic phenotype of viral epitope-specific CD8 T cells precludes memory development and is an intrinsic property of the epitope

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Immunology and Virology; Department of Pathology

Date

10-8-2004

Document Type

Article

Medical Subject Headings

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 Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: J Immunol. 2004 Oct 15;173(8):5138-47.

Related Resources

Link to Article in PubMed

Journal Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

15470058