SPONTANEOUS AND ANTIBODY DIRECTED CYTOTOXICITY OF DOUBLE-NEGATIVE T-CELLS FROM AUTOIMMUNE MICE

MRL/Mp-lpr/lpr (MRL/lpr) mice develop a syndrome similar to systemic lupus erythematosus in humans. This strain of mice is characterized by the progressive accumulation of CD4-CD8-(double-negative; DN) T cells which express increased levels of cell adhesion molecules such as CD44 and heat stable antigen (HSA). The DN T cells exhibited a higher level of spontaneous cytolytic activity and contained a higher level of serine esterase as compared with T cells of MRL/Mp-+/+ (MRL/+) mice. We also found that mAbs against CD44, Mel-14, CD45R, and HSA could augment the cytolytic activity of DN T cells of MRL/lpr mice. Antibody-mediated augmentation of cytolytic activity of DN T cells was due to conjugate formation in which the Fc portion of mAb bound to the Fc-gamma receptor on target cells and the Fab portion of mAb bound to corresponding cell surface antigens on DN T cells. The antibody-mediated augmentation of cytolytic activity was not detected in T cells of MRL/+ mice and lymphokine activated killer (LAK) cells of C57BL/6 mice. In contrast, anti-CD3 mAbs could augment the cytolytic activity of DN T cells, T cells as well as LAK cells. mAbs against LFA-1 and VLA-4 failed to augment the cytolytic activity of three different effector cells. It should be noted that anti-CD3 mAb-mediated cytolytic activity of DN T cells was substantially reduced by anti-LFA-1 mAb. However, CD44, Mel-14, CD45R as well as HSA-mediated cytolytic activity of DN T cells was not inhibited by anti-LFA-1 mAb. The cell - cell and cell - matrix interactions through cell adhesion molecules might augment the antigen non-specific cytolytic activity of DN T cells in vivo.