HLA-A2-matched peripheral blood mononuclear cells from type 1 diabetic patients, but not nondiabetic donors, transfer insulitis to NOD-scid/γc(null)/HLA-A2 transgenic mice concurrent with the expansion of islet-specific CD8+ T cells.
HLA-A2-matched peripheral blood mononuclear cells from type 1 diabetic patients, but not nondiabetic donors, transfer insulitis to NOD-scid/γc(null)/HLA-A2 transgenic mice concurrent with the expansion of islet-specific CD8+ T cells.
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DOI：
10.2337/db10-1287
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发表时间：
2011-06
期刊：
影响因子：
7.7
通讯作者：
Frelinger JA
中科院分区：
文献类型：
--
作者：
Whitfield-Larry F;Young EF;Talmage G;Fudge E;Azam A;Patel S;Largay J;Byrd W;Buse J;Calikoglu AS;Shultz LD;Frelinger JA
Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing β-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. We adoptively transferred HLA-A2–matched peripheral blood mononuclear cells (PBMCs) from type 1 diabetic patients and nondiabetic control subjects into transgenic NOD-scid/γcnull/HLA-A*0201 (NOD-scid/γcnull/A2) mice. 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/γcnull/A2 mice after transfer. 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/γcnull/A2 mice. Lymphocytes from type 1 diabetic patients preferentially infiltrate the islets of NOD-scid/γcnull/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 identified epitope-specific CD8+ T cells among the islet infiltrates. We show that insulitis is transferred to NOD-scid/γcnull/A2 mice that received HLA-A2–matched PBMCs from type 1 diabetic patients. In addition, many of the infiltrating CD8+ T cells are epitope-specific and produce interferon-γ after in vitro peptide stimulation. This indicates that NOD-scid/γcnull/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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DOI：
10.1073/pnas.0932778100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Lieberman, SM;Evans, AM;DiLorenzo, TP
通讯作者：
DiLorenzo, TP
影响因子：
15.9
作者：
Skowera, Ania;Ellis, Richard J.;Peakman, Mark
通讯作者：
Peakman, Mark
DOI：
10.1084/jem.20081720
发表时间：
2009-06-08
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Strowig T;Gurer C;Ploss A;Liu YF;Arrey F;Sashihara J;Koo G;Rice CM;Young JW;Chadburn A;Cohen JI;Münz C
通讯作者：
Münz C
影响因子：
8.6
作者：
King, Marie;Pearson, Todd;Greiner, Date L.
通讯作者：
Greiner, Date L.
影响因子：
2.6
作者：
Nervi, Bruno;Rettig, Michael P.;DiPersio, John F.
通讯作者：
DiPersio, John F.