Differential modulation of CD8 beta by rat gamma delta and alpha beta T cells after activation

Major histocompatibility complex (MHC) class I-restricted alpha beta T cell s express the CD8 alpha beta heterodimer, which acts as a MHC class I-speci fic co-receptor. Rats are so far the only species with frequent expression of the CD8 alpha beta by MHC-Lin restricted gamma delta T cells. This study compares CD8 alpha beta expression by splenic rat alpha beta and gamma del ta T cells and reveals a lineage-specific difference in the control or CD8 beta expression. After activation in vitro. many gamma delta T cells, but n ot alpha beta T cells. persistently down-modulate the expression of CD8 bet a, but not CD8 alpha, at the RNA level. Down-regulation occurred after stim ulation with T-cell receptor (TCR)-specific monoclonal antibody (mAb) and i nterleukin-2 (IL-2) or CD28-mediated costimulation. and after activation wi th phorbol 12-myristate 13-acetate (PMA) and ionomycin. Functional differen ces between modulating and non-modulating cells were not found with respect to interferon-gamma (IFN-gamma) production and cytolytic activity. The mod ulation could be indicative for a fundamental difference between alpha beta and gamma delta T cells and also limits the use of CD8 beta as a stable ma rker of gamma delta T-cell subsets. Possibly. CD8 beta modulation provides a mechanism to escape over-stimulation by (auto-)antigens by increasing the threshold of TCR-mediated activation in gamma delta T cells.