Cell surface expression of the 300 kDa mannose-6-phosphate receptor by activated T lymphocytes

Phosphosugars, such as mannose-6-phosphate (M6P), have been shown previousl y to display anti-inflammatory properties, notably inhibition of experiment al autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis in rat s. It has been proposed that M6P exerts its anti-inflammatory effect by dis placing lysosomal enzymes, which are involved in T-cell extravasation into inflammatory sites, from the 300 kDa mannose-6- phosphate receptor (MPR-300 ) on the surface of T cells. If this model is correct MPR-300 should be sel ectively expressed on the surface of activated T cells, as T cell entry int o the central nervous system in EAE depends on the T cells being in an acti vated state. Thus, the present study examines whether cell surface expressi on of MPR-300 by T lymphocytes correlates with their state of activation an d whether T cells in inflammatory sites express the receptor. Flow cytometr ic studies showed MPR-300 to be absent from the surface of unstimulated rat T cells isolated from peripheral blood and lymphoid tissues, and T cells r esident within the peritoneal cavity. In contrast, MPR-300 was expressed on activated T cells derived from an inflammatory peritoneal exudate. In vitr o studies demonstrated transient expression of MPR-300 on the surface of sp lenic T cells following stimulation with Con A. MPR-300 was also induced on T-cell lines by antigen stimulation. These data demonstrate that T cells i n inflammatory sites express MPR-300 on their surface and activation of T l ymphocytes induces cell surface expression of MPR-300. Such findings are co nsistent with the hypothesis that cell surface MPR-300 is required for the entry of T cells into inflammatory sites.