T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury.
T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury.
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T细胞的免疫突触诱导体内和体外脑星形胶质细胞极化：一种新型的星形胶质细胞反应机制对细胞损伤。
DOI：
10.1371/journal.pone.0002977
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发表时间：
2008-08-20
期刊：
影响因子：
3.7
通讯作者：
Lowenstein, Pedro R.
中科院分区：
文献类型：
--
作者：
Barcia, Carlos;Sanderson, NicholasS. R.;Barrett, Robert J.;Wawrowsky, Kolja;Kroeger, Kurt M.;Puntel, Mariana;Liu, Chunyan;Castro, Maria G.;Lowenstein, Pedro R.
星形胶质细胞通常通过细胞肥大对创伤、中风或神经变性做出反应，然而，它们对T细胞特异性免疫攻击的反应知之甚少。效应T细胞在从大脑清除病毒感染的细胞期间与靶细胞建立特异性接触，称为免疫突触。免疫突触介导T细胞和靶细胞之间的细胞间通讯，在体外和体内。靶病毒感染的星形胶质细胞如何响应由效应T细胞建立的免疫突触的形成尚不清楚。在此，我们证明，作为T细胞攻击的结果，受感染的星形胶质细胞发生了显着的形态学变化。从正常的多极细胞，它们变成单极，向效应T细胞形成的免疫突触延伸一个主要突起，并撤回大部分更精细的过程。因此，靶星形胶质细胞变得朝向接触的T细胞极化。细胞极性的组织者MTOC位于突起的基部，高尔基体堆积分布在整个突起中，向免疫突触的远端延伸。因此，抗病毒T细胞不是引起星形胶质细胞肥大，而是引起靶病毒感染的星形胶质细胞的主要结构重组。星形胶质细胞极化，而不是肥大，响应于T细胞攻击可能是由于T细胞提供了一个非常集中的攻击，因此，星形胶质细胞以极化的方式响应。使用体外同种异体模型也检测到高尔基体堆叠朝向接触T细胞的类似极化。因此，不同的T细胞能够诱导靶星形胶质细胞的极化。靶星形胶质细胞响应于免疫突触的极化可以在调节星形胶质细胞对攻击效应T细胞的响应的结果中起重要作用，无论是在体内和体外抗病毒（例如在HIV、HTLV-1、HSV-1或LCMV感染期间感染）、抗移植、自身免疫或抗肿瘤免疫应答期间。
Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown. Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes. Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV infection), anti-transplant, autoimmune, or anti-tumor immune responses in vivo and in vitro.
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影响因子：
5.4
作者：
Brossard, C;Feuillet, V;Trautmann, A
通讯作者：
Trautmann, A
DOI：
10.3109/15419069309097256
发表时间：
1993-01-01
期刊：
CELL ADHESION AND COMMUNICATION
影响因子：
--
作者：
FURER, M;HARTLOPER, V;NATH, A
通讯作者：
NATH, A
影响因子：
64.5
作者：
Etienne-Manneville, S;Hall, A
通讯作者：
Hall, A
影响因子：
5.3
作者：
Bushong, EA;Martone, ME;Ellisman, MH
通讯作者：
Ellisman, MH
影响因子：
--
作者：
Barcia, Carlos;Gerdes, Christian;Lowenstein, Pedro R.
通讯作者：
Lowenstein, Pedro R.