We have shown that human platelet factor 4 alleviates Con A-induced or pneumococcal-specific immunosuppression in mice, an effect of potential clinical value. The activity can be removed from human or mouse serum or platelet releasates by T cells of the suppressor phenotype, and suppressor cells can be removed from spleen cell suspensions by """"""""planning"""""""" on PF4-coated surfaces. If serine protease activity is arrested immediately after the platelets have secreted the releasates and PF4 prepared from it are not active, although the amount of PF4 measured by radioimmunoassay is not affected. Monoclonal antibodies will be sought that identify activity and used in an attempt to develop an in vitro assay. The enzymatic changes that activate PF4 will be established and the enzyme localized in platelet organelles and characterized. Cells with receptors for PF4 will be identified in human an mouse blood, spleen or lymph nodes by sue of fluorescence cell analysis with PF4 and antibodies to PF4 and the cells will be characterized with monoclonal antibodies to surface determinants. The binding kinetics of active radiolabeled PF4 to T cells of the suppressor phenotype will be assessed. Since PF4 does not act on suppression in vitro, it may sequester suppressor cells away from lymphoid organs, e.g., on the heparan sulfate on vascular endothelium. Therefore, the distribution of III indium-labeled T cells of the suppressor phenotype will be explored with and without PF4 and/or heparin injection.
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