Journal Title or Book Title
The Journal of Clinical Investigation
The JCI is an open access journal. All research content is freely available immediately upon publication, and all articles published in the JCI are deposited in PubMed Central (PMC). Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles under the "fair use" limitations of US copyright law. https://doi.org/10.1172/JCI13605
Susceptibility to immune-mediated diabetes (IMD) in humans and NOD mice involves their inherently defective T cell immunoregulatory abilities. We have followed natural killer (NK) T cell numbers in patients with IMD, both by flow cytometry using mAbs to the characteristic junctions found in the T cell receptors of this cell subtype, and by semiquantitative RT-PCR for the corresponding transcripts. Both before and after clinical onset, the representation of these cells in patients’ PBMCs is reduced. We also report low numbers of resting CD4+ CD25+ T cells in IMD patients, a subset of T cells shown to have important immunoregulatory functions in abrogating autoimmunities in 3-day thymectomized experimental mice. Whereas a biased Th1 to Th2 cytokine profile has been suggested to underlie the pathogenesis of IMD in both species, we found defective production of IFN-γ in our patients after in vitro stimulation of their PBMCs by phorbol-myristate acetate and ionomycin and both IFN-γ and IL-4 deficiencies in Vα24+ NK T–enriched cells. These data suggest that multiple immunoregulatory T (Treg) cell defects underlie islet cell autoimmunity leading to IMD in humans and that these lesions may be part of a broad T cell defect.
Sanz, Maureen M.; Kukreja, Anjli; Cost, Giulia; Marker, John; Zhang, Chenhui; Lin-Su, Karen; Sun, Zhong; Ten, Svetlana; Exley, Mark; Wilson, Brian; and Porcelli, Steven, "Multiple immuno-regulatory defects in type-1 diabetes" (2002). Faculty Works: Biology, Chemistry, and Environmental Studies. 28.