When This Quality Control Mechanism Fails, Tumors Escape The Body's Defenses Or Autoimmune Diseases Develop

BOSTON -- May 11, 1999 -- Researchers at Dana-Farber Cancer Institute and Harvard Medical School have identified a mechanism the immune system uses to detect and eliminate dysfunctional T cells. Reported in the May 14 Science, the study clarifies a long-standing puzzle about the development of systemic autoimmune diseases and has immediate practical implications for how to design cancer vaccines.

Harvey Cantor, chair of the Department of Cancer Immunology and AIDS at DFCI and an HMS professor of pathology, and his colleagues have found that the peripheral immune system plays an important role in the selection of properly functioning T cells. Until recently, this process was thought to occur only in the thymus.

As nascent T lymphocytes emerge from the bone marrow, they enter the thymus gland. The thymus identifies promising infection fighters by selecting T cells able to recognize and lightly bind the body's own peptides, presented by MHC proteins. The thymus then eliminates those cells that bind self antigen too tightly, to prevent autoimmune reactions. At this point, typically only two types of mature T cells are left: Helper T cells and cytotoxic cells. Helper T cells carrying the CD 4 coreceptor recognize antigen bound by class 2 MHC molecules and trigger antibody production upon activation by foreign peptides. Cytotoxic cells carry CD 8, recognize antigen bound to class 1 proteins, and kill cells bearing foreign peptides.

But nothing in biology is foolproof. The thymus does allow into the periphery some CD 8 misfits that recognize class 2-bound antigen, as well as incompetent cells that cannot recognize MHC molecules at all. Since these cells could be dangerous, immunologists have wondered how the body deals with them.

Cantor and his colleagues isolated mouse CD 8 cells unable to re
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Contact: Bill Schaller
schaller@hms.harvard.edu
617-432-0441
Harvard Medical School
14-May-1999