ADOPTIVE TRANSFER OF DIABETES INTO IMMUNODEFICIENT NOD-SCID SCID MICE - RELATIVE CONTRIBUTIONS OF CD4+ AND CD8+ T-CELLS FROM DIABETIC VERSUS PREDIABETIC NOD.NON-THY-1A DONORS
ADOPTIVE TRANSFER OF DIABETES INTO IMMUNODEFICIENT NOD-SCID SCID MICE - RELATIVE CONTRIBUTIONS OF CD4+ AND CD8+ T-CELLS FROM DIABETIC VERSUS PREDIABETIC NOD.NON-THY-1A DONORS
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DOI：
10.2337/diabetes.42.1.44
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发表时间：
1993-01-01
期刊：
影响因子：
7.7
通讯作者：
LEITER, EH
中科院分区：
文献类型：
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作者：
CHRISTIANSON, SW;SHULTZ, LD;LEITER, EH
从NOD小鼠中CD4和CD8 T细胞子集在糖尿病的产物转移中的作用的精确定义使内源性T细胞可能被募集的可能性变得复杂。两个新创建的点头股票，点头。NON-NON-THY-1A和点头/LTSZ-SCID，分别用作T细胞供体和接收者，以消除内源性T细胞的贡献，从而定义转移的要求T细胞子集是NOD供体中潜在的糖尿病发育的函数。由糖尿病前期或糖尿病的点数制备的总T细胞和T细胞子集，将thy-la的供体分析转移到6周龄的NOD-SCID/SCID接受者中，该供体受到监测的糖尿病发育。收养转移后，受体脾脏和胰腺的流式细胞仪和组织学分析均表明供体的淋巴细胞（THY1.1+）的起源。来自糖尿病和糖尿病前供体的总T细胞和富集的CD4+ T细胞制剂将糖尿病转移到了点头/SCID/SCID受体中。然而，当从糖尿病前供体和糖尿病供体中分离CD4+淋巴细胞时，糖尿病发作的平均时间加倍，并且随着时间的推移，这些转移因产生小但大量的CD8+细胞而变得复杂。仅富集的CD8+种群就无法转移疾病。通过抗CD4+细胞接受者的抗CD8 MoAb治疗对CD8+细胞的更严格排除表明，糖尿病患者与非糖尿病供体的CD4+淋巴细胞的糖尿病生成效率显着差异。从糖尿病供体的富含CD4+淋巴细胞的富含CD4+淋巴细胞的受体中，糖尿病被顺从转移到58％。相比之下，糖尿病前供体的富集CD4+淋巴细胞的接受者都没有在体内摩押治疗后出现糖尿病。 T细胞种群在T-SCID/SCID接受者中产生严重的胰岛炎和唾液炎的能力与其诱导糖尿病的能力紧密相似。为了通过抑制巨噬细胞迁移到胰岛抑制胰岛炎，点头/SCID小鼠与二氧化硅与糖尿病供体的T细胞的收养转移结合在一起。慢性二氧化硅处理未能消耗组织巨噬细胞，并且在未分流的T细胞转移后不能阻止糖尿病的发育。讨论了证据，表明在没有CD8+ T细胞子集的情况下，与年龄相关的CD4+ T细胞能力差异是通过了CD4+淋巴细胞的长期暴露于Beta-cell抗原的函数。捐助者。这项研究证实，CD4+和CD8+ T细胞都需要启动NOD小鼠的β细胞破坏。
Precise definition of the role of both CD4 and CD8 T-cell subsets from NOD mice in the adoptive transfer of diabetes has been complicated by the possibility that endogenous T-cells may be recruited. Two newly created NOD congenic stocks, NOD.NON-Thy-1a and NOD/LtSz-scid, have been used as T-cell donors and recipients, respectively, to eliminate contributions from endogenous T-cells and thus to define the requirement for transferred T-cell subsets as a function of underlying diabetes development in the NOD donor. Total T-cells and T-cell subsets prepared from either prediabetic or diabetic NOD.NON-Thy-la donors were adoptively transferred into 6-wk-old NOD-scid/scid recipients that were monitored for diabetes development. Both flow cytometric and histological analysis of recipient spleen and pancreas after adoptive transfer showed lymphocytes of donor (Thy1.1+) origin exclusively. Total T-cell and enriched CD4+ T-cell preparations from both diabetic and young prediabetic donors transferred diabetes to NOD-scid/scid recipients. However, the mean time to diabetes onset was doubled when CD4+ lymphocytes were isolated from prediabetic versus diabetic donors, and these transfers were complicated by the generation of small but significant numbers of CD8+ cells over time. Enriched CD8+ populations alone were unable to transfer disease. More rigorous exclusion of CD8+ cells by means of anti-CD8 MoAb treatment in vivo of the recipients of enriched CD4+ cells demonstrated a significant difference in the diabetogenic potency of CD4+ lymphocytes from diabetic versus nondiabetic donors. Diabetes was adoptively transferred to 58% of the recipients of enriched CD4+ lymphocytes from diabetic donors. In contrast, none of the recipients of enriched CD4+ lymphocytes from young prediabetic donors developed diabetes after MoAb treatment in vivo. The ability of a T-cell population to produce severe insulitis and sialitis in NOD-scid/scid recipients of T-cells closely paralleled its ability to induce diabetes. In an effort to suppress insulitis by suppression of macrophage migration to the islets, NOD-scid/scid mice were with silica in conjunction with adoptive transfer of T-cells from diabetic donors. Chronic silica treatment failed to deplete tissue macrophages and did not prevent diabetes development after transfer of unfractionated T-cells. Evidence is discussed indicating that the age-associated differences in ability of CD4+ T-cells to adoptively transfer diabetes in the absence of the CD8+ T-cells subset is a function of prior, chronic exposure of the CD4+ lymphocytes to beta-cell antigens in the donor. This study confirms that both CD4+ and CD8+ T-cells are required to initiate beta-cell destruction in NOD mice.