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HY-TCR转基因小鼠中的胸腺哺育细胞多细胞复合体证明了它们与MHC限制的关联。

Thymic nurse cell multicellular complexes in HY-TCR transgenic mice demonstrate their association with MHC restriction.

作者信息

Martinez Marcia, Samms Michael, Hendrix Tonya M, Adeosun Oluwaseun, Pezzano Mark, Guyden Jerry C

机构信息

Biology Department, Tuskegee University, Tuskegee, Alabama 36088, USA.

出版信息

Exp Biol Med (Maywood). 2007 Jun;232(6):780-8.

PMID:17526770
Abstract

This study examines thymic nurse cell (TNC) function during T-cell development. It has been suggested that TNCs function in the removal of nonfunctional and/or apoptotic thymocytes and do not participate in major histocompatibility complex restriction. We analyzed TNCs isolated from both normal C57BL/6 mice and C57BL/6 TgN (TCRHY) mice (HY-TCR transgenic mice). Using confocal microscopic analyses of TNCs isolated from C57BL/6 animals, we showed that 75%-78% of the enclosed thymocyte subset was viable, and 87%-90% of these cells expressed both CD4 and CD8. CD4 and CD8 also were expressed on TNC thymocytes isolated from both male and female HY-TCR transgenic mice. The transgenic female thymus was shown to have 17 times more TNCs per milligram of thymus than the transgenic male thymus. TNCs from HY-TCR transgenic females were 8-10 microm larger than transgenic male TNCs, and the female TNCs contained five times more thymocytes within intracytoplasmic vacuoles, with less than 4% apoptosis. However, more than 42% of the thymocytes within transgenic male TNCs were apoptotic. The large number and size of TNCs containing viable thymocytes in the female transgenic thymus suggest that TNC function is not limited to the removal of apoptotic thymocytes. We believe that the selective uptake of viable double-positive thymocytes by TNCs in C57BL/6 and HY-TCR transgenic female mice provides evidence that this interaction occurs during the process of major histocompatibility complex restriction.

摘要

本研究检测了T细胞发育过程中胸腺哺育细胞(TNC)的功能。有人提出,TNC的功能是清除无功能和/或凋亡的胸腺细胞,且不参与主要组织相容性复合体限制。我们分析了从正常C57BL/6小鼠和C57BL/6 TgN(TCRHY)小鼠(HY-TCR转基因小鼠)分离出的TNC。通过对从C57BL/6动物分离出的TNC进行共聚焦显微镜分析,我们发现,被包裹的胸腺细胞亚群中有75%-78%是活细胞,其中87%-90%的细胞同时表达CD4和CD8。从雄性和雌性HY-TCR转基因小鼠分离出的TNC胸腺细胞也表达CD4和CD8。结果显示,转基因雌性小鼠每毫克胸腺中的TNC数量比转基因雄性小鼠多17倍。来自HY-TCR转基因雌性小鼠的TNC比转基因雄性TNC大8-10微米,雌性TNC的胞质内液泡中所含胸腺细胞数量是雄性的五倍,凋亡细胞少于4%。然而,转基因雄性TNC中的胸腺细胞凋亡率超过42%。雌性转基因胸腺中含有活胸腺细胞的TNC数量众多且体积较大,这表明TNC的功能不限于清除凋亡胸腺细胞。我们认为,C57BL/6和HY-TCR转基因雌性小鼠中TNC对活的双阳性胸腺细胞的选择性摄取证明,这种相互作用发生在主要组织相容性复合体限制过程中。

相似文献

1
Thymic nurse cell multicellular complexes in HY-TCR transgenic mice demonstrate their association with MHC restriction.HY-TCR转基因小鼠中的胸腺哺育细胞多细胞复合体证明了它们与MHC限制的关联。
Exp Biol Med (Maywood). 2007 Jun;232(6):780-8.
2
Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene.在表达bcl-2转基因的T细胞受体转基因小鼠中T细胞的阳性和阴性选择
Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1376-80. doi: 10.1073/pnas.91.4.1376.
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Thymic nurse cells exclusively bind and internalize CD4+CD8+ thymocytes.胸腺哺育细胞专门结合并内化CD4⁺CD8⁺胸腺细胞。
Cell Immunol. 1992 Apr;140(2):495-506. doi: 10.1016/0008-8749(92)90214-a.
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Abnormal thymocyte development and production of autoreactive T cells in T cell receptor transgenic autoimmune mice.T细胞受体转基因自身免疫小鼠中胸腺细胞发育异常及自身反应性T细胞的产生。
J Immunol. 1991 Jul 15;147(2):466-74.
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Circulating macrophages as well as developing thymocytes are enclosed within thymic nurse cells.循环巨噬细胞以及发育中的胸腺细胞被包裹在胸腺哺育细胞内。
Cell Immunol. 2001 Aug 25;212(1):16-23. doi: 10.1006/cimm.2001.1836.
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Thymic nurse cells provide microenvironment for secondary T cell receptor α rearrangement in cortical thymocytes.胸腺滋养细胞为皮质胸腺细胞中次级 T 细胞受体α重排提供微环境。
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20572-7. doi: 10.1073/pnas.1213069109. Epub 2012 Nov 27.
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The T cell receptor repertoire of CD4-8+ thymocytes is altered by overexpression of the BCL-2 protooncogene in the thymus.胸腺中BCL-2原癌基因的过表达会改变CD4-8+胸腺细胞的T细胞受体库。
J Exp Med. 1994 Jan 1;179(1):145-53. doi: 10.1084/jem.179.1.145.
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Lysosomal-mediated degradation of apoptotic thymocytes within thymic nurse cells.胸腺哺育细胞内溶酶体介导的凋亡胸腺细胞降解。
Cell Immunol. 1999 Nov 1;197(2):108-15. doi: 10.1006/cimm.1999.1559.
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Ligand-stimulated signaling events in immature CD4+CD8+ thymocytes expressing competent T-cell receptor complexes.表达有功能的T细胞受体复合物的未成熟CD4⁺CD8⁺胸腺细胞中的配体刺激信号事件。
Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9949-53. doi: 10.1073/pnas.88.22.9949.
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Precommitment of CD4+CD8+ thymocytes to either CD4 or CD8 lineages.CD4+CD8+胸腺细胞向CD4或CD8谱系的预先定向。
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8982-6. doi: 10.1073/pnas.90.19.8982.

引用本文的文献

1
Thymic Nurse Cells Participate in Heterotypic Internalization and Repertoire Selection of Immature Thymocytes; Their Removal from the Thymus of Autoimmune Animals May be Important to Disease Etiology.胸腺哺育细胞参与未成熟胸腺细胞的异型内化和受体库选择;从自身免疫动物胸腺中去除它们可能对疾病病因学很重要。
Curr Mol Med. 2015;15(9):828-35. doi: 10.2174/1566524015666151026102328.
2
The Antigenic Determinant That Defines Thymic Nurse Cells Is Expressed by Thymic Epithelial Progenitor Cells.定义胸腺哺育细胞的抗原决定簇由胸腺上皮祖细胞表达。
Front Cell Dev Biol. 2014 Apr 28;2(13). doi: 10.3389/fcell.2014.00013.
3
The importance of the nurse cells and regulatory cells in the control of T lymphocyte responses.
滋养细胞和调节细胞在控制 T 淋巴细胞应答中的重要性。
Biomed Res Int. 2013;2013:352414. doi: 10.1155/2013/352414. Epub 2012 Dec 26.
4
The thymus microenvironment in regulating thymocyte differentiation.胸腺微环境调控胸腺细胞分化。
Cell Adh Migr. 2010 Jul-Sep;4(3):382-90. doi: 10.4161/cam.4.3.11789. Epub 2010 Jul 15.
5
Thymic nurse cells exhibit epithelial progenitor phenotype and create unique extra-cytoplasmic membrane space for thymocyte selection.胸腺滋养细胞呈现上皮祖细胞表型,并为胸腺细胞选择创造独特的细胞外膜空间。
Cell Immunol. 2010;261(2):81-92. doi: 10.1016/j.cellimm.2009.11.004. Epub 2009 Dec 24.