title: Role of CD45 signaling pathway in galactoxylomannan-induced T cell damage.
abstract: Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45(+/+) and CD45(-/-) cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45(+/+) cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45(-/-) cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis.
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Pericolini
authors.forename: Elena
authors.initials: E
authors.lastname: Gabrielli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bistoni
authors.forename: Elio
authors.initials: E
authors.lastname: Cenci
authors.forename: Stefano
authors.initials: S
authors.lastname: Perito
authors.forename: Siu-Kei
authors.initials: SK
authors.lastname: Chow
authors.forename: Francesca
authors.initials: F
authors.lastname: Riuzzi
authors.forename: Rosario
authors.initials: R
authors.lastname: Donato
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: Anna
authors.initials: A
authors.lastname: Vecchiarelli
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003455:Cryptococcus neoformans / Q000378:metabolism; D015870:Gene Expression; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; C043689:galactoxylomannan; D017493:Leukocyte Common Antigens