In Vivo T Cell Signaling Leading to Apoptosis vs. Cytokine Production
Abstract
Two signals are hypothesized as necessary for the activation of T cells leading tocytokine production. The first signal is delivered by the T cell receptor (TCR) and thesecond by a costimulatory signal., the best defined being CD28 and its homologue CTLA-4(cytotoxic T lymphocyte associated protein-four). Treatment of T cells with antibodiesagainst the invariant CD3-e chain of the TCR-CD3 complex is a widely used model for Tcell activation and is being considered as an immune suppressant for clinical trials. sincemitogenic anti-CD3 antibodies administered in vivo induce T cell tolerance and depletion.Although extensive studies have been performed with anti-CD3 antibodies, little is knownconcerning the mechanisms involved in either anti-CD3 antibody-induced cytokineproduction or subsequent T cell depletion in vivo. Previous studies have suggested threepossible fates for T cells stimulated by anti-CD3 antibodies: TCR blockade or modulation.functional nonresponsiveness or anergy., and apoptosis. In this investigation three assayswere adapted to detect apoptosis of peripheral T cells. My findings suggest that anti-CD3antibody-induced peripheral T cell depletion results from apoptosis following high but notlow dose administration ofanti-CD3 antibodies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 17, 1995
- Accession Number
- AD1011477
Entities
People
- Jeffrey J. Adamovicz
Organizations
- Uniformed Services University of the Health Sciences