CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
批准号:
6030747
负责人:
William James Waldman
金额:
$10.22万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-08-01 至 2000-06-30
关键词:
MHC class I antigen MHC class II antigen T cell receptor arteriosclerosis blocking antibody cardiovascular transplantation cell adhesion molecules cell cell interaction cell cycle cell migration cell population study clinical research cytokine cytolysis cytomegalovirus cytotoxic T lymphocyte flow cytometry human subject immune tolerance /unresponsiveness immunoprecipitation immunosuppressive mixed tissue /cell culture protein structure function vascular endothelium virus infection mechanism
中文摘要
巨细胞病毒(CMV)被认为是恶性肿瘤的加重剂
英文摘要
Cytomegalovirus (CMV) has been implicated as an exacerbating agent in the
development of transplantation-associated arteriosclerosis (TxAA), a
major limitation in long-term cardiac allograft survival for which no
satisfactory medical intervention is yet available. In an effort to
define mechanisms explaining this association, we propose that CMV-
infected graft endothelia can initiate a host immune activation cascade,
and that the consequent localized release of cytokines can raise proximal
uninfected endothelium to a state of enhanced alloimmunogenicity, ideally
poised for immune attack by circulating host cellular immune components.
Thus the experiments described in this proposal are designed to test the
hypotheses that 1) CMV-infected endothelial cells (EC) can stimulate the
generation of allogeneic and autologous cytolytic T cells (CTL) which
exhibit promiscuous lytic activity against uninfected EC, 2) that these
interactions occur by non-traditional mechanisms which are highly
dependent upon costimulatory signals, 3) that uninfected endothelia
activated by cytokines elaborated by CMV-responsive T cells can serve as
a substrate for T cell transmigration and/or cytolysis, and 4) that these
events can occur to a significant extent in the presence of clinically
relevant concentrations of immunosuppressive agents. CTL precursor
frequencies will be determined for populations of in vitro-stimulated T
cells by measurement of radiolabel release from 51Cr-labelled infected
or uninfected autologous or allogeneic EC targets. To determine the
contribution of HLA and adhesion molecules in these responses, stimulator
and/or target populations will be depleted of HLA class I and/or HLA
class II-positive cells immunomagnetically or by fluorescence-activated
cell sorting, or assayed for cytolysis in the presence of blocking
antibodies. immunofluorescence flow cytometry will be used to identify
responsive T cell subsets as naive or memory, alpha/Beta or gamma/delta,
as well as by Vbeta type. Finally, to simulate CMV-triggered cytokine-
mediated events which may occur at the graft/host interface, endothelial
monolayers will be activated by culture beneath trans-well inserts
containing T cells in combination with CMV-infected EC, then tested for
their ability to promote trans-endothelial T cell migration and their
susceptibility to CTL-mediated lysis in the absence or presence of
various concentrations of clinically relevant immunosuppressive agents.
Results of these studies will elucidate aspects of protective and/or
pathogenic immune responses to this virus, potentially identify
heretofore undescribed pathways of immune activation, and help elucidate
the role of CMV in the development of transplantation-associated
arteriosclerosis.
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DOI:
10.1097/00007890-199909270-00014
发表时间:
1999-09
期刊:
Transplantation
影响因子:
6.2
作者:
[Waldman Wj;Deborah A. Knight;N. Lurain;Daniel M. Miller;Daniel D. Sedmak;James W. Williams;Anita S. Chong]
通讯作者:
Waldman Wj;Deborah A. Knight;N. Lurain;Daniel M. Miller;Daniel D. Sedmak;James W. Williams;Anita S. Chong
Attenuation of cytomegalovirus-induced endothelial intercellular adhesion molecule-1 mRNA/protein expression and T lymphocyte adhesion by a 2'-O-methoxyethyl antisense oligonucleotide.
2-O-甲氧基乙基反义寡核苷酸可减弱巨细胞病毒诱导的内皮细胞间粘附分子-1 mRNA/蛋白表达和 T 淋巴细胞粘附。
DOI:
10.1097/00007890-200002150-00019
发表时间:
2000
期刊:
Transplantation
影响因子:
6.2
作者:
[Knight,DA, Briggs,BR, Bennett,CF, Harindranath,N, Waldman,WJ, Sedmak,DD]
通讯作者:
Sedmak,DD
Cytolytic activity against allogeneic human endothelia: resistance of cytomegalovirus-infected cells and virally activated lysis of uninfected cells.
针对同种异体人内皮细胞的细胞溶解活性:巨细胞病毒感染细胞的抗性和未感染细胞的病毒激活裂解。
DOI:
10.1097/00007890-199807150-00011
发表时间:
1998
期刊:
Transplantation
影响因子:
6.2
作者:
[Waldman,WJ, Knight,DA, Adams,PW]
通讯作者:
Adams,PW
An in vitro model of T cell activation by autologous cytomegalovirus (CMV)-infected human adult endothelial cells: contribution of CMV-enhanced endothelial ICAM-1.
自体巨细胞病毒 (CMV) 感染的人成体内皮细胞激活 T 细胞的体外模型:CMV 增强的内皮 ICAM-1 的贡献。
DOI:
--
发表时间:
1998
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
作者:
[Waldman,WJ, Knight,DA, Huang,EH]
通讯作者:
Huang,EH
T-cell activation response to allogeneic CMV-infected endothelial cells is not prevented by ganciclovir or foscarnet: implications for transplant vascular sclerosis.
更昔洛韦或膦甲酸不能阻止对同种异体 CMV 感染的内皮细胞的 T 细胞激活反应:对移植血管硬化的影响。
DOI:
10.1097/00007890-200201270-00032
发表时间:
2002
期刊:
Transplantation
影响因子:
6.2
作者:
[Waldman,WJames, LeClaire,JoshuaD, Knight,DeborahA]
通讯作者:
Knight,DeborahA
Endothelial-reactive antibodies: a diagnostic test for Susac's syndrome
-
批准号:8048660
-
项目类别:
-
资助金额:$26.69万
-
财政年份:2010
-
负责人:William James Waldman
-
依托单位:
Endothelial-reactive antibodies: a diagnostic test for Susac's syndrome
-
批准号:8133697
-
项目类别:
-
资助金额:$14.95万
-
财政年份:2010
-
负责人:William James Waldman
-
依托单位:
Antiviral activity of leflunomide against respiratory syncytial virus
-
批准号:7908439
-
项目类别:
-
资助金额:$30.0万
-
财政年份:2009
-
负责人:William James Waldman
-
依托单位:
Antiviral activity of leflunomide against respiratory syncytial virus
-
批准号:7679336
-
项目类别:
-
资助金额:$30.76万
-
财政年份:2008
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6708845
-
项目类别:
-
资助金额:$28.32万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6287600
-
项目类别:
-
资助金额:$29.15万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
CMV DISRUPTION OF CONSTITUTIVE MHC CLASS II
-
批准号:6690776
-
项目类别:
-
资助金额:$25.81万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6632026
-
项目类别:
-
资助金额:$28.32万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
ANTIVIRAL ACTIVITY OF THE IMMUNOSUPPRESSANT LEFLUNOMIDE
-
批准号:6510888
-
项目类别:
-
资助金额:$28.07万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
CMV DISRUPTION OF CONSTITUTIVE MHC CLASS II
-
批准号:6626385
-
项目类别:
-
资助金额:$26.26万
-
财政年份:2001
-
负责人:William James Waldman
-
依托单位:
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
-
批准号:2234994
-
项目类别:
-
资助金额:$9.92万
-
财政年份:1996
-
负责人:William James Waldman
-
依托单位:
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
-
批准号:2445342
-
项目类别:
-
资助金额:$10.01万
-
财政年份:1996
-
负责人:William James Waldman
-
依托单位:
CMV/IMMUNE INTERACTIONS IN TRANSPLANT ARTERIOSCLEROSIS
-
批准号:2735318
-
项目类别:
-
资助金额:$10.01万
-
财政年份:1996
-
负责人:William James Waldman
-
依托单位:
海外基金