STIMULATION OF T-CELLS VIA CD44 REQUIRES LEUKOCYTE-FUNCTION-ASSOCIATED ANTIGEN INTERACTIONS AND INTERLEUKIN-2 PRODUCTION

This article reports the results of the analysis of the activation sig nals delivered to T and B cells by means of the CD44 molecule and an a gonistic mAb, i.e., CB05 mAb, which is able to induce cell activation and aggregation upon binding. The functional effects culminate in T-ce ll proliferation in the presence of autologous accessory cells. Such e ffects are barely detectable in thymocytes, while B cells prove refrac tory to the action of the agonistic mAb. All of these events have been followed by the expression of surface activation markers, by the tran scription of selected cytokine genes (IFN-gamma, IL-4, and GM-CSF), an d by the secretion of IL-2. Cell activation via CD44 has been evaluate d as to its relationship with CD3 and CD2 activation pathways, proving synergistic with the latter. The CD44 signaling is protein kinase dep endent. Furthermore, the role of surface molecules as cosig nals in th e CD44 pathway has been analyzed, showing that CD11a (and its ligand C D54), HLA class I, and CD25 are instrumental in the implementation of( a) efficient activation/proliferation signals and (b) a potent cytotox ic potential.