Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase-deficient mouse model of human hyper-IgD syndrome (HIDS).
Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase-deficient mouse model of human hyper-IgD syndrome (HIDS).
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DOI：
10.1007/s10545-011-9349-x
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发表时间：
2012-01
影响因子：
4.2
通讯作者：
Gibson, K. Michael
中科院分区：
文献类型：
--
作者：
Hager, Elizabeth J.;Piganelli, Jon D.;Tse, Hubert M.;Gibson, K. Michael
我们试图确定甲羟戊酸激酶缺陷型高IgD综合征（HIDS）小鼠模型脾脏淋巴细胞群的激活状态和增殖能力。我们以前报道过，鼠甲羟戊酸激酶基因切除对纯合子突变体是胚胎致死的，而杂合子（Mvk+/−）表现出人类HIDS的几种表型特征，包括血清IgD、伊加和TNFα水平升高、体温失调、血液学异常和脾肿大。T和B淋巴细胞和巨噬细胞群体的细胞表面活化标记物的流式细胞术分析表明，在所有研究的脾细胞类型中B7糖蛋白的异常表达。在基础状态（未刺激）和伴刀豆球蛋白A（Con-A）体外刺激全脾细胞培养物后，观察到Mvk+/−和Mvk+/+同窝对照之间的表达水平差异。在Mvk+/− CD 4和CD 8 T细胞中，观察到CD 25、CD 80、CD 152和CD 28表达的改变。Mvk+/−脾巨噬细胞表达的CD 80、CD 86、CD 40和CD 11 c水平发生改变，而Mvk+/− B淋巴细胞的CD 40、CD 80和CD 86表达存在差异。Mvk+/−脾细胞亚群也表现出对体外刺激的增殖能力改变。我们推测，活化，增殖和调节免疫应答的强度和持续时间所必需的细胞表面蛋白表达的不平衡可能导致我们的模型和潜在的人类HIDS中T细胞活化，增殖和效应功能缺陷。
We sought to determine the activation status and proliferative capacities of splenic lymphocyte populations from a mevalonate kinase-deficient mouse model of hyper-IgD syndrome (HIDS). We previously reported that murine mevalonate kinase gene ablation was embryonic lethal for homozygous mutants while heterozygotes (Mvk+/−) demonstrated several phenotypic features of human HIDS including increased serum levels of IgD, IgA, and TNFα, temperature dysregulation, hematological abnormalities, and splenomegaly. Flow cytometric analysis of cell surface activation markers on T and B lymphocytes, and macrophage populations, demonstrated aberrant expression of B7 glycoproteins in all splenic cell types studied. Differences in expression levels between Mvk+/− and Mvk+/+ littermate controls were observed in both the basal state (unstimulated) and after Concanavalin A (Con-A) stimulation in vitro of whole splenocyte cultures. In Mvk+/− CD4 and CD8 T cells, alterations in expression of CD25, CD80, CD152, and CD28 were observed. Mvk+/− splenic macrophages expressed altered levels of CD80, CD86, CD40, and CD11c while Mvk+/− B lymphocytes had differential expression of CD40, CD80, and CD86. Mvk+/− splenocyte subpopulations also exhibited altered proliferative capacities in response to in vitro stimulation. We postulate that imbalances in the expression of cell surface proteins necessary for activation, proliferation, and regulation of the intensity and duration of an immune response may result in defective T cell activation, proliferation, and effector functions in our model and potentially in human HIDS.
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DOI：
10.1084/jem.178.6.2185
发表时间：
1993-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Freeman GJ;Borriello F;Hodes RJ;Reiser H;Gribben JG;Ng JW;Kim J;Goldberg JM;Hathcock K;Laszlo G
通讯作者：
Laszlo G
影响因子：
4.4
作者：
Li, Ruobing;Perez, Nicolas;Vasu, Chenthamarakshan
通讯作者：
Vasu, Chenthamarakshan
DOI：
10.1107/s0907444901001895
发表时间：
2001-04-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Davis, SJ;Ikemizu, S;Stuart, DI
通讯作者：
Stuart, DI
影响因子：
32.4
作者：
KEARNEY, ER;PAPE, KA;JENKINS, MK
通讯作者：
JENKINS, MK
影响因子：
4.2
作者：
Hager, E. J.;Tse, H. M.;Gibson, K. M.
通讯作者：
Gibson, K. M.