CD59 AND CD48 EXPRESSED BY RAT RETINAL-PIGMENT EPITHELIAL-CELLS ARE MAJOR LIGANDS FOR THE CD2-MEDIATED ALTERNATIVE PATHWAY OF T-CELL ACTIVATION

The alternative CD2-mediated pathway of T cell activation, which is in dependent of MHC/peptide recognition by the TCR/CD3 complex, is depend ent upon two signals being received by the CD2 molecule. The natural l igand for CD2 is CD58, but controversy exists over alternative or addi tional ligands that could deliver the second signal in vive. We have u sed rat retinal pigment epithelial cells (RPE), which lack temperature -insensitive ligands for CD2 adhesion, to study Ag-independent T cell activation, Rat RPE cells expressed high levels of CD59 and low levels of another potential CD2 ligand, CD48, both in vitro and in the in vi vo model of experimental autoimmune uveoretinitis. When increasing num bers of syngeneic T cells were added to microwell cultures of rat RPE cells, the T cells, even in the absence of any exogenous stimulant in the cultures, underwent spontaneous proliferation. This effect require d metabolically active RPE cells, and was IL-2 driven and enhanced in the presence of indomethacin. Proliferation was modulated by phosphati dylinositol-phospholipase C treatment of the RPE, and blocked by mAbs to CD59. Ab cross-linking of CD48 but not CD59 on the RPE was found to induce messenger RNA expression for IL-1 beta, which together with co nstitutively expressed IL-6 are required costimulatory factors for T c ell activation through CD2. This is the first demonstration in a fully syngeneic system that bi-directional signaling involving CD59 and CD4 8 molecules expressed by physiologically normal, nonhematopoeitic, cel ls can trigger T lymphocyte activation and proliferation through autoc rine IL-2 production in the absence of Ag.