Differential modulation of CD8beta by rat gammadelta and alphabeta T cells after activation

Major histocompatibility complex (MHC) class I-restricted alphabeta T cells express the CD8alphabeta heterodimer, which acts as a MHC class I-specific co-receptor. Rats are so far the only species with frequent expression of the CD8alphabeta by MHC-unrestricted gammadelta T cells. This study compares CD8alphabeta expression by splenic rat alphabeta and gammadelta T cells and reveals a lineage-specific difference in the control of CD8beta expression. After activation in vitro, many gammadelta T cells, but not alphabeta T cells, persistently down-modulate the expression of CD8beta, but not CD8alpha, at the RNA level. Down-regulation occurred after stimulation with T-cell receptor (TCR)-specific monoclonal antibody (mAb) and interleukin-2 (IL-2) or CD28-mediated costimulation, and after activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Functional differences between modulating and non-modulating cells were not found with respect to interferon-gamma (IFN-gamma) production and cytolytic activity. The modulation could be indicative for a fundamental difference between alphabeta and gammadelta T cells and also limits the use of CD8beta as a stable marker of gammadelta T-cell subsets. Possibly, CD8beta modulation provides a mechanism to escape over-stimulation by (auto-)antigens by increasing the threshold of TCR-mediated activation in gammadelta T cells.