Mechanisms for induction of L-selectin loss from T lymphocytes by a cryptococcal polysaccharide, glucuronoxylomannan

Disseminated cryptococcosis is accompanied by cryptococcal polysaccharides in the serum and the lack of cellular infiltrates in infected tissues. Cryp tococcal polysaccharides given intravenously to mice inhibit the influx of T lymphocytes into the sites of cell-mediated immune response. The focus he re was to determine whether cryptococcal polysaccharides modulate the expre ssion of molecules, such as L-selectin, that are important in extravasation of T cells. Cryptococcal glucuronoxylomannan (GXM), but not galactoxyloman nan or mannoprotein, was found to cause loss of L-selectin from freshly iso lated human T cells of both CD4 and CD8 subsets and from Jurkat cells. With the signaling-pathway inhibitors staurosporine (which inhibits protein kin ase C) and herbimycin A (which inhibits protein tyrosine kinases), we showe d that GXM or the cryptococcal culture filtrate antigen CneF directly induc es L-selectin loss from CD4(+) and CD8(+) T cells via a herbimycin A-sensit ive pathway(s) presumably involving one or more protein tyrosine kinases bu t not via a pathway involving protein kinase C. Loss of L-selectin from the T cells before the T cells have a chance to bind to L-selectin ligands on endothelial cells mould be expected to prevent T-cell migration into inflam ed tissues and/or lymph organs.