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Cited by 640

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Multiple immuno-regulatory defects in type-1 diabetes

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Anjli Kukreja, Giulia Cost, John Marker, Chenhui Zhang, Zhongsheng Sun, Karen Lin‐Su, Svetlana Ten, Maureen M. Sanz, Mark A. Exley, Brian Wilson, Steven Anthony Porcelli, Noel Keith Maclaren·2002·Journal of Clinical Investigation
DOI 10.1172/jci13605
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Abstract

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-gamma in our patients after in vitro stimulation of their PBMCs by phorbol-myristate acetate and ionomycin and both IFN-gamma and IL-4 deficiencies in V(alpha)24(+) 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.

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Metadata

Authors
Kukreja, A., Cost, G., Marker, J., Zhang, C., Sun, Z., Lin‐Su, K., Ten, S., Sanz, M. M., Exley, M. A., Wilson, B., Porcelli, S. A., & Maclaren, N. K.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2002-01-01
Volume
109
Issue
1
Pages
131-140
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci13605
OpenAlex
W2168419126
Cited by
640
References
1
FWCI
24.68
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Multiple immuno-regulatory defects in type-1 diabetes. https://app.cochat.ai/papers/10.1172/jci13605
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Kukreja, A., Cost, G., Marker, J., Zhang, C., Sun, Z., Lin‐Su, K., Ten, S., Sanz, M. M., Exley, M. A., Wilson, B., Porcelli, S. A., & Maclaren, N. K. (2002). Multiple immuno-regulatory defects in type-1 diabetes. Journal of Clinical Investigation. https://doi.org/10.1172/jci13605

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