CD45 modulates galectin-1-induced T cell death: Regulation by expression of core 2 O-glycans

Galectin-1 induces death of immature thymocytes and activated T cells. Gale ctin-1 binds to T cell-surface glycoproteins CD45, CD43, and CD7, although the precise roles of each receptor in cell death are unknown. We have deter mined that CD45 can positively and negatively regulate galectin-1-induced T cell death, depending on the glycosylation status of the cells. CD45(+) BW 5147 T cells lacking the core 2 beta -1,6-N-acetylglucosaminyltransferase ( C2GnT) were resistant to galectin-1 death. The inhibitory effect of CD45 in C2GnT(-) cells appeared to require the CD45 cytoplasmic domain, because Re v1.1 cells expressing only CD45 transmembrane and extracellular domains wer e susceptible to galectin-1 death. Moreover, treatment with the phosphotyro sine-phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanad ate(V) enhanced galectin-1 susceptibility of CD45(+) T cell lines, but had no effect on the death of CD45(-) T cells, indicating that the CD45 inhibit ory effect involved the phosphatase domain. Expression of the C2GnT in CD45 (+) T cell lines rendered the cells susceptible to galectin-1, while expres sion of the C2GnT in CD45- cells had no effect on gaIectin-1 susceptibility . When CD45(+) T cells bound to galectin-1 on murine thymic stromal cells, only C2GnT(+) T cells underwent death. On C2GnT(+) cells, CD45 and gaIectin -1 co-localized in patches on membrane blebs while no segregation of CD45 w as seen on C2GnT- T cells, suggesting that oligosaccharide-mediated cluster ing of CD45 facilitated galectin-1-induced cell death.