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Natural occurrence of thymocytes that react with myelin basic protein

Department of Neurology (Dr. Steinman), Stanford University, Stanford, CA, the Department of Cell Biology (Dr. Cohen), and the Department of Chemical Immunology (Dr. Teitelbaum), Weizmann Institute of Science, Rehovot, Israel.

In adult strain 13 guinea pigs, two lines of evidence show that there are natural autoreactive thymocytes that can react with myelin basic protein (BP) or the encephalitogenic nonapeptide (EP). An autoradiographic binding assay revealed antigen-specific receptors for ¹²⁵I-BP on thymocytes. A ³H-thymidine antigen-specific proliferation assay demonstrated that normal thymocytes were activated by EP- or BP-pulsed macrophages. Soluble BP suppressed the activation of thymocytes by macrophage-associated BP. The mode of presentation of BP or EP, whether macrophage-associated or soluble, may be critical in maintaining self-tolerance and preventing an autoimmune attack on the central nervous system.

Address correspondence and reprint requests to Dr. Steinman, Department of Neurology, Stanford University, Stanford, CA 94305.

Accepted for publication October 2, 1979.

Presented as the S. Weir Mitchell Award paper by Dr. Steinman at the thirty-first annual meeting of the American Academy of Neurology, Chicago, IL, April 1979.

Dr. Steinman was a recipient of an NIH postdoctoral fellowship. This research was financed by Contract 931 awarded to Dr. Irun Cohen, Department of Cell Biology, Weizmann Institute of Science, and to Dr. David Holtzman, Department of Neurology, Stanford University, from the United States-Israel Binational Science Foundation, National Science Foundation.