A regulatory defect that drives lupus has been identified by a group of scientists.
Correcting the defect 'may represent an effective therapeutic approach to systemic lupus erythematosus-like autoimmune disease,' according to researchers at Dana-Farber Cancer Institute in Cambridge, Mass., and Jackson Laboratory scientists.
The research team was led by Harvey Cantor, chair of the department of cancer immunology and AIDS at Dana-Farber, in collaboration with the laboratory of Jackson Professor Derry Roopenian.
Most autoimmune diseases strike specific organs, such as the pancreas in type1 diabetes. Lupus, however, is a systemic disease in which abnormal antibodies are produced throughout the body, inflaming a variety of tissues and organs, including the skin, heart, lungs, kidneys and brain.
Follicular T helper (TFH) cells fuel B cells to produce antibodies, which can be useful in fighting infections. But in lupus, TFH fuel B cells that produce dangerous antibodies that attack normal tissues (autoantibodies).
CD8+ T cells ("killer T cells"), on the other hand, normally attack and destroy only infected cells.
Cantor and colleagues discovered that a small, but critically important, population of CD8+ T cells (less than 5 percent), plays a specialized role in protecting from lupus.
These so-called CD8+ T regulatory, or Treg, cells are specially equipped to destoy TFH cells, and by doing so, prevent lupus from developing.
Using a mouse model for systemic lupus erythematosus in humans, the research team found defects in CD8+ Treg activity.
he research was published in the Proceedings of the National Academy of Sciences.