GSBS Student Publications

Title

Lymphocyte apoptosis during the silencing of the immune response to acute viral infections in normal, lpr, and Bcl-2-transgenic mice

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Department of Pathology; Department of Molecular Genetics and Microbiology

Date

7-1-1995

Document Type

Article

Medical Subject Headings

Acute Disease; Animals; *Apoptosis; Cell Death; Cells, Cultured; Down-Regulation; Flow Cytometry; Immunohistochemistry; Leukocyte Count; Lymphocytes; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Lymphoproliferative Disorders; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Spleen

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

This report examines the mechanisms involved in the down-regulation of the immune response in acute viral infection and documents the presence of apoptotic lymphocytes in situ in the spleens of mice during the resolution of the immune response to acute lymphocytic choriomeningitis virus infection. Apoptotic cells were detected by an in situ nucleotidyl transferase assay. Both T and B lymphocytes were shown to be dying in vivo, the latter in clusters. A biphasic occurrence of apoptosis during the course of the acute infection was observed, with elevated levels occurring at day 3 after infection and a second more pronounced peak at day 11 after infection, coincident with the decline of the cytotoxic T lymphocyte response and with the decrease in total splenic leukocyte number. Apoptosis in vivo was detected in lpr mice, suggesting that Fas expression is not imperative for lymphocyte apoptosis in the context of an acute viral infection. Apoptosis in situ and the decline of the T lymphocyte response to acute lymphocytic choriomeningitis virus infection was unaffected by the enforced lymphocyte-directed expression of Bcl-2, a protein that blocks growth factor deprivation-induced apoptosis of lymphocytes in vitro. These results argue that the silencing of the T cell response to acute infection may not be a result simply of growth factor deprivation. The susceptibility of activated T cells to apoptotic death, which has previously been associated with virus-induced immune deficiency, may therefore also explain the en masse elimination of the expanded lymphocyte pool subsequent to an acute viral infection.

Rights and Permissions

Citation: Am J Pathol. 1995 Jul;147(1):79-91.

Related Resources

Link to article in PubMed

Journal Title

The American journal of pathology

PubMed ID

7604887