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Infection and Immunity, January 1999, p. 220-229, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mechanisms for Induction of L-Selectin Loss from T Lymphocytes by a Cryptococcal Polysaccharide, Glucuronoxylomannan

Zhao Ming Dong, Lydgia Jackson, and Juneann W. Murphy^*

Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma

Received 18 December 1997/Returned for modification 23 January 1998/Accepted 1 October 1998

Disseminated cryptococcosis is accompanied by cryptococcal polysaccharides in the serum and the lack of cellular infiltrates in infected tissues. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of T lymphocytes into the sites of cell-mediated immune response. The focus here was to determine whether cryptococcal polysaccharides modulate the expression of molecules, such as L-selectin, that are important in extravasation of T cells. Cryptococcal glucuronoxylomannan (GXM), but not galactoxylomannan or mannoprotein, was found to cause loss of L-selectin from freshly isolated human T cells of both CD4 and CD8 subsets and from Jurkat cells. With the signaling-pathway inhibitors staurosporine (which inhibits protein kinase C) and herbimycin A (which inhibits protein tyrosine kinases), we showed that GXM or the cryptococcal culture filtrate antigen CneF directly induces L-selectin loss from CD4⁺ and CD8⁺ T cells via a herbimycin A-sensitive pathway(s) presumably involving one or more protein tyrosine kinases but 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 would be expected to prevent T-cell migration into inflamed tissues and/or lymph organs.

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^* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK 73190. Phone: (405) 271-3110. Fax: (405) 271-3117. E-mail: juneann-murphy{at}ouhsc.edu.

Present address: Center for Blood Research, Harvard Medical School, Boston, MA 02115.

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Infection and Immunity, January 1999, p. 220-229, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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