DEFECTS IN MONOCYTE POLARIZATION AND DENDRITIC CELL CLUSTERING IN PATIENTS WITH GRAVES-DISEASE - A PUTATIVE ROLE FOR A NONSPECIFIC IMMUNOREGULATORY FACTOR RELATED TO RETROVIRAL P15E

A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent infections of the respiratory tract and in various types of malignancies. These impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; < 25 kDa) circulating in the serum of the patients. The factor, which seems to be a non-specific immunoregulatory factor, shares a structural homology with pl5E, the capsular protein of murine and feline leukaemogenic retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendritic cells of Graves' patients, monocytes were isolated from the peripheral blood and dendritic cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogeneic lymphocytes. A defective fMLP-induced monocyte polarization was found (16 vs 37% in healthy controls), whereas the dendritic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of < 25kDa prepared from the serum of Graves' patients on healthy donor monocytes and dendritic cells was studied to test the presence of pl5E-like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendritic cell clustering. A mixture of two monoclonal antibodies directed against p15E was able to neutralize these suppressive effects. The relationship of this pl5E-like factor occurring in the serum of Graves' patients to the recently reported - genomic expression of retroviral sequences in thyrocytes/leucocytes of Obese Strain chickens and Graves' patients (ev 22, HIV gag) needs further clarification.