T Cell Tolerance

Giles F. Filley Lecture

¹ Departments of Biochemistry Biophysics and Genetics, Microbiology, University of Colorado Health Science Center, Denver., The Department of Medicine, Howard Hughes Medical Institute, National Jewish Center for Immunology and Respiratory Medicine
² The Department of Medicine, Howard Hughes Medical Institute, National Jewish Center for Immunology and Respiratory Medicine
³ Departments of Immunology and Medicine, University of Colorado Health Science Center, Denver., The Department of Medicine, Howard Hughes Medical Institute, National Jewish Center for Immunology and Respiratory Medicine

T cell tolerance to self is induced by several mechanisms. Immature T cells may die, and mature T cells may die or be inactivated by contact with self. While we do not understand completely what governs which of these courses will be adopted by an autoreactive T cell, 2 points are clear. Self is in part distinguished from nonself by the fact that the former is always present, while the latter is only intermittently in the body. Secondly, it seems that the default response for T cells is "off" rather than "on." That is, peripheral T cells will become tolerant to antigen unless some other phenomenon such as adjuvant triggers them to respond.

One other point should be mentioned. In spite of the power of the mechanisms which causes self tolerance, tolerance is not complete. Autoreactive T cells specific for cryptic antigens, expressed in the brain or eye for example, can easily be demonstrated. Many autoimmune diseases may be caused by aberrant activation and exposure to target organ of these cells, rather than failure of the normal mechanisms of tolerance themselves.