Denise Faustman - Research

Research

Faustman's current research is based on the observation that autoreactive T cells, that is, T cells programmed to attack the body's own cells and tissues, are more sensitive than normal T cells to the effects of TNF-alpha (TNF-α), a cytokine that influences the immune system. Under some conditions, TNF-α causes T cells to undergo apoptosis, or programmed cell death. Faustman's hypothesis, contrary to conventional thinking, is that blocking TNF-α actually promotes the survival of undesirable autoreactive T cells, and that certain autoimmune diseases can be treated by stimulating TNF-α to trigger apoptosis in autoimmune T cells. TNF-α is a strong promoter of inflammation, and several treatments have been developed to block the effects of TNF-α in chronic and autoimmune diseases, including adalimumab, infliximab, and etanercept. However, side effects of these drugs can include new-onset autoimmunity and flare-ups of autoimmune symptoms.

Faustman's approach was tested in non-obese diabetic mice (NOD mice), a strain of mice that spontaneously develops type 1 diabetes. Injecting the mice with a common inflammatory agent that increases the production of TNF-α, called complete Freund's adjuvant (CFA), and a preparation of spleen cells reversed type 1 diabetes in mice with end-stage disease and allowed the beta islet cells to regenerate.

Faustman hypothesized that this regeneration may be attributed in part to the re-differentiation of the spleen cells - that although the splenic stem cells they identified were not obligatory for regeneration to occur, these cells could hasten regeneration. The source of islet cell regeneration is debated. Researchers from three laboratories funded by the Juvenile Diabetes Research Foundation confirmed that Dr. Faustman's protocol can successfully reverse type 1 diabetes in end-stage mice; however, they did not find that the splenic cells played a role and suggested that the source of islet cell regeneration was proliferation of existing pancreatic islet cells.

A research group led by a researcher from the U.S. National Institutes of Health (NIH) has also replicated Faustman's work in mice with type 1 diabetes. This group found that adult stem cells from the spleen did play a role in regeneration and also that Faustman's protocol could be used to reverse a second autoimmune disease, called Sjögren's syndrome, in mice.