Title

Comprehensive early and lasting loss of memory CD8 T cells and functional memory during acute and persistent viral infections

UMMS Affiliation

Department of Pathology

Publication Date

2-24-2004

Document Type

Article

Subjects

Acute Disease; Animals; CD8-Positive T-Lymphocytes; Cell Survival; Chronic Disease; Cytotoxicity, Immunologic; Epitopes, T-Lymphocyte; *Immunologic Memory; Kinetics; Lymphocyte Count; Lymphocytic Choriomeningitis; Lymphopenia; Male; Mice; Mice, Inbred C57BL; Nuclear Proteins; Peritoneum; Pichinde virus; T-Lymphocyte Subsets; Time Factors; Vaccinia virus; Vesicular stomatitis Indiana virus; Viral Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Viral infections have been shown to induce lymphopenias that lower memory CD8 T cell frequencies, and they also have been shown to cause a permanent loss of memory cells specific to previously encountered pathogens. In this study, the patterns and significance of virus-induced memory CD8 T cell depletion were examined in mice immune to heterologous (Pichinde, vesicular stomatitis, vaccinia) viruses and subsequently challenged with acute or persistent lymphocytic choriomeningitis virus infections. Memory CD8 T cell loss was comprehensive and occurred in both lymphoid and peripheral tissues of the immune host. The impact of the loss of memory T cells was reflected by in vivo cytotoxicity assays, which showed decreased clearance of epitope-expressing targets. Memory CD8 T cell loss occurred very early (day 2) after infection, and was thereafter sustained, consistent more with an active deletion model than with a competition model. Cross-reactive T cells, in contrast, increased in number, but memory cells were reduced whether or not there was competition from cross-reactive T cells. Memory T cell loss was more profound during persistent infection than after acute infection. Adoptive transfer studies showed that, unlike the resolved acute infection, in which the reduced memory frequencies became stable, memory T cell loss was a continuously ongoing process during persistent infection. This study therefore links an early virus-induced lymphopenia to a subsequent long-term loss of CD8 T cell memory and offers a new mechanism for immune deficiency during persistent viral infections.

Rights and Permissions

Citation: J Immunol. 2004 Mar 1;172(5):3139-50.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

14978120