Abstract: The current invention relates to an active factor present in homogenized brain tissue which inhibits antigen-driven proliferation of lymphocytes in culture, but stimulates proliferation in response to most mitogens. The inhibitory activity can be destroyed by treatment with proteases or neuraminadase. The activity is in the insoluble fraction of the homogenate, but becomes soluble in 0.04 M NaOH. After gel filtration chromatography of the NaOH soluble material, the suppressive activity is in the high molecular weight fraction which elutes in the void volume of the column. This fraction contains protein and carbohydrate. The activity is not affected by neutralizing antibodies against regulatory cytokines, does not depend on Fas or FasL, and is not due to the presence of gangliosides. These data suggest that a brain glycoprotein which is either membrane-bound or part of the extracellular matrix has powerful immune regulatory effects in culture.