Journal article
HLA-A2--matched peripheral blood mononuclear cells from type 1 diabetic patients, but not nondiabetic donors, transfer insulitis to NOD-scid/[gamma][c.sup.null]/HLA-A2 transgenic mice concurrent with the expansion of islet-specific [CD8.sup.+] T cells.(ORIGINAL ARTICLE)
Diabetes (New York, N.Y.), v 60(6), p1726
01 Jun 2011
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
OBJECTIVE--Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing [beta]-cells. NOD mice provide a useful tool for understanding disease pathogenesis and progression. Although much has been learned from studies with NOD mice, increased understanding of human type 1 diabetes can be gained by evaluating the pathogenic potential of human diabetogenic effector cells in vivo. Therefore, our objective in this study was to develop a small-animal model using human effector cells to study type 1 diabetes. RESEARCH DESIGN AND METHODS--We adoptively transferred HLA-A2-matched peripheral blood mononuclear cells (PBMCs) from type 1 diabetic patients and nondiabetic control subjects into transgenie NOD-scid/[sub.[gamma][c.sup.null]/HLA-A*0201 (NOD-scid/ [gamma][c.sup.null]/A2) nuce. At various times after adoptive transfer, we determined the ability of these mice to support the survival and proliferation of the human lymphoid cells. Human lymphocytes were isolated and assessed from the blood, spleen, pancreatic lymph node and islets of NOD-scid/[gamma][c.sup.null]/A2 mice after transfer. RESULTS--Human T and B cells proliferate and survive for at least 6 weeks and were recovered from the blood, spleen, draining pancreatic lymph node, and most importantly, islets of NOD-scid/[gamma][c.sup.null]/A2 mice. Lymphocytes from type 1 diabetic patients preferentially infiltrate the islets of NOD-scid/[gamma][c.sup.null]/A2 mice. In contrast, PBMCs from nondiabetic HLA-A2-matched donors showed significantly less islet infiltration. Moreover, in mice that received PBMCs from type 1 diabetic patients, we identiffed epitope-specific [CD8.sup.+] T cells among the islet infiltrates. CONCLUSIONS--We show that insulitis is transferred to NODscid/[gamma][c.sup.null]/A2 mice that received HLA-A2-matched PBMCs from type 1 diabetic patients. In addition, many of the infiltrating [CD8.sup.+] T cells are epitope-specific and produce interferon-[gamma] after in vitro peptide stimulation. This indicates that NOD-scid/[gamma][c.sup.null]/A2 mice transferred with HLA-A2-matched PBMCs from type 1 diabetic patients may serve as a useful tool for studying epitope-specific T-cell-mediated responses in patients with type 1 diabetes.
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- Title
- HLA-A2--matched peripheral blood mononuclear cells from type 1 diabetic patients, but not nondiabetic donors, transfer insulitis to NOD-scid/[gamma][c.sup.null]/HLA-A2 transgenic mice concurrent with the expansion of islet-specific [CD8.sup.+] T cells.(ORIGINAL ARTICLE)
- Creators
- Fatima Whitfield-Larry - University of North Carolina at Chapel HillEllen F Young - University of North Carolina at Chapel HillGarrick Talmage - University of North Carolina at Chapel HillElizabeth Fudge - University of North Carolina at Chapel HillAnita Azam - University of North Carolina at Chapel HillShipra Patel - University of North Carolina at Chapel HillJoseph LargayWarren ByrdJohn Buse - University of North Carolina at Chapel HillAli S CalikogluLeonard D Shultz - Jackson LaboratoryJeffrey A Frelinger - University of North Carolina at Chapel Hill
- Publication Details
- Diabetes (New York, N.Y.), v 60(6), p1726
- Publisher
- American Diabetes Association
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000291369600010
- Scopus ID
- 2-s2.0-79959484284
- Other Identifier
- 991021448059504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism