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The Journal of Immunology, 2001, 167: 5697-5707.
Copyright © 2001 by The American Association of Immunologists

CD45 Modulates Galectin-1-Induced T Cell Death: Regulation by Expression of Core 2 O-Glycans1

Julie T. Nguyen*, Douglas P. Evans*, Marisa Galvan*, Karen E. Pace*, David Leitenberg{ddagger}, Thanhmy N. Bui* and Linda G. Baum2,*,{dagger}

* Department of Pathology and Laboratory Medicine and {dagger} The Jonsson Comprehensive Cancer Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095; and {ddagger} Department of Immunology, George Washington University, School of Medicine, Washington, DC 20037

Galectin-1 induces death of immature thymocytes and activated T cells. Galectin-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 determined that CD45 can positively and negatively regulate galectin-1-induced T cell death, depending on the glycosylation status of the cells. CD45+ BW5147 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 Rev1.1 cells expressing only CD45 transmembrane and extracellular domains were susceptible to galectin-1 death. Moreover, treatment with the phosphotyrosine-phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate(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 inhibitory effect involved the phosphatase domain. Expression of the C2GnT in CD45+ T cell lines rendered the cells susceptible to galectin-1, while expression of the C2GnT in CD45- cells had no effect on galectin-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 galectin-1 co-localized in patches on membrane blebs while no segregation of CD45 was seen on C2GnT- T cells, suggesting that oligosaccharide-mediated clustering of CD45 facilitated galectin-1-induced cell death.




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