The RT6 rat lymphocyte alloantigen circulates in soluble form

RT6 is a rat maturational lymphocyte alloantigen that appears to subserve important immunoregulatory functions. The lymphopenic diabetes-prone BioBreeding (BB)/Worcester rat is severely deficient in RT6+ T cells and develops spontaneous autoimmune diabetes mellitus. Transfusion of RT6+ T cells prevents the disease. Conversely, in vivo immune elimination of RT6+ T cells from the diabetes-resistant line of BB rats induces diabetes and thyroiditis. RT6 protein is expressed in two allotypic forms, each linked to the cell surface by a phosphatidylinositol (PI) anchor. The mechanism by which RT6+ T cells exert their regulatory function is not known, nor is the function of the RT6 protein defined. In this study, we investigated the possibility that, like other PI-linked proteins, RT6 also exists in a soluble form in the circulation. Using standard biochemical procedures we observed: (i) Soluble RT6 circulates in readily detectable amounts in all rat strains studied. (ii) The diabetes-prone BB rat circulates less RT6.1 than does any other strain, including the coisogenic diabetes-resistant line. (iii) Injections of monoclonal anti-RT6.1 antibody rapidly eliminate soluble RT6 from the circulation of diabetes resistant BB rats. The existence of a soluble form of a protein associated with immunoregulatory T cells suggests the possibility that soluble RT6 itself might possess immunomodulatory properties.