An alkali-soluble factor present in normal brain tissue inhibits antigen-specific lymphocyte proliferation

The brain has long been recognized as an immune privileged site and probably contains multiple immune regulatory factors. We have investigated the immune regulatory properties of brain tissue on cultured lymphocytes. Homogenized brain tissue inhibits proliferation to antigen, but stimulates proliferation in response to most mitogens. The inhibitory activity is 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 alkali soluble material, the suppressive activity is in the high molecular weight fraction which contains protein and carbohydrate. The brain homogenate blocks the effects of IL-2. 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 or proteoglycan which is either membrane-bound or part of the extracellular matrix has immune regulatory effects in culture. The relevance of these findings to immune regulation in the intact animal deserves further investigation.