STIMULATION THROUGH CD50 (ICAM-3) INDUCES BOTH ACTIVATION AND PROGRAMMED CELL-DEATH OF HUMAN THYMOCYTES

CD50 (ICAM-3) has identified as the third CD11a/CD18 (LFA-1) counter r eceptor. We investigated the expression and possible role of this mole cule in the induction of early and late activation events in human thy mocytes. We observed that CD50 expression is acquired by early T cell progenitors (CD34(+)) and maintained during thymic development, reachi ng the highest levels in the most mature population thymocytes (CD3(hi gh)). Neither basal nor cytokine-induced expression of CD50 was observ ed on untransformed human thymic epithelial cell lines. Cross-linking of CD50 expressed on the surface of human thymocytes, by using mAbs re cognizing epitopes not related to the CD11a binding site, transduced t ransmembrane signals leading to an increase of intracellular calcium c oncentration. This calcium mobilization was inhibited when CD50 was co -cross-linked with CD45, suggesting that tyrosine phosphorylation is a lso involved in CD50 signaling. the same anti-CD50 mAbs that were able to affect intracellular calcium levels were shown to induce CD69 but not CD25 expression on human thymocytes. This effect was preferentiall y observed on CD3(low)/CD3(high) thymocyte subpopulations. Cross-linki ng of CD50 also significantly increased activation-induced cell death of human thymocytes. These results support the idea that CD50 molecule can play a role in developing functionally mature T lymphocytes.