The authors developed a novel assay to examine T cell responses to a panel of epitopes naturally expressed by islet cells and demonstrated that it is the pathways of T cell differentiation and maturation in reaction to these epitopes in T1DM patients (in whom autoimmunity develops) and normal individuals (in whom autoimmunity is arrested) that are different. Upon exposure to antigen, naïve T cells in normal individuals differentiate into T cells that produce IL-10, and possibly TGF- beta, subsequently inhibiting cells that would normally mediate an aggressive immune response. The results reported by Peakman and colleagues suggest that in patients with T1DM, there is instead induction of a predominant number of T cells that produce IFN-gamma and IL-2, which drives an autoaggressive immune response. Why these T cell activation pathways differ between normal and T1DM patients will require further characterization.
In an accompanying commentary, Kevan Herald from the Naomi Berrie Diabetes Center at Columbia University, New York, comments that "these new findings concerning the responses of normal individuals and patients with T1DM to autoantigens shed light on the differences in immune responses between these two groups and the mechanisms of pathogenesis of the disease. The findings suggest ways in which regulation of the autoimmune response occur and offer approaches to immune modulation and ultimately tolerance, the immunologist's "Holy Grail."
TITLE: Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health
AUTHOR CONTACT:
Mark Peakman
King's College London, London, United Kingdom.
Phone: 44-207-955-4656
Fax: 44-207-955-8894
E-mail: mark.peakman@kcl.ac.uk
View the PDF of this article at: http://www.jci.org/cgi/content/full/113/3/451
ACCOMPANYING COMMENTARY: Achieving antigen-specific immune regulation
AUTHOR CONTACT:
Kevan C. Herold
Naomi Berrie Diabetes Center, Columbia University, New York, New York, USA.
Phone: (212) 305-3171
Fax: (212) 851-5493
E-mail: kh318@columbia.edu
Journal of Clinical Investigation