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. 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.
Nguyen
J T
JT
Department of Pathology and Laboratory Medicine and The Jonsson Comprehensive Cancer Center, University of California, School of Medicine, Los Angeles 90095, USA.
Evans
D P
DP
Galvan
M
M
Pace
K E
KE
Leitenberg
D
D
Bui
T N
TN
Baum
L G
LG
D000818:Animals; D017209:Apoptosis; D037483:Galectin 1; D017353:Gene Deletion; D006388:Hemagglutinins / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000502:physiology; D011134:Polysaccharides / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017154:Stromal Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D037483:Galectin 1; D006388:Hemagglutinins; D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases; D017493:Leukocyte Common Antigens