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A novel multimeric form of FasL modulates the ability of diabetogenic T cells to mediate type 1 diabetes in an adoptive transfer model.

Authors
  • Franke, Deanna D H
  • Yolcu, Esma S
  • Alard, Pascale
  • Kosiewicz, Michele M
  • Shirwan, Haval
Type
Published Article
Journal
Molecular Immunology
Publisher
Elsevier
Publication Date
Apr 01, 2007
Volume
44
Issue
11
Pages
2884–2892
Identifiers
PMID: 17324464
Source
Medline
License
Unknown

Abstract

Activation induced cell death (AICD) via Fas/FasL is the primary homeostatic molecular mechanism employed by the immune system to control activated T-cell responses and promote tolerance to self-antigens. We herein investigated the ability of a novel multimeric form of FasL chimeric with streptavidin (SA-FasL) having potent apoptotic activity to induce apoptosis in diabetogenic T cells and modulate insulin-dependent type 1 diabetes (IDDM) in an adoptive transfer model. Diabetogenic splenocytes from NOD/Lt females were co-cultured in vitro with SA-FasL, SA control protein, or alone without protein, and adoptively transferred into NOD/Lt-Rag1(null) recipients for diabetes development. All animals receiving control (Alone: n=16 or SA: n=17) cells developed diabetes on average by 6 weeks, whereas animals receiving SA-FasL-treated (n=25) cells exhibited significantly delayed progression (p<.001) and decreased incidence (70%). This effect was associated with an increase in CD4(+)CD25(+) T cells and correlated with FoxP3 expression in pancreatic lymph nodes. Extracorporeal treatment of peripheral blood lymphocytes using SA-FasL during disease onset represents a novel approach that may alter the ability of pathogenic T cells to mediate diabetes and have therapeutic utility in clinical management of IDDM.

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