FAS/CD95 AND HIV-1 INDUCED HEMATOPATHOLOGY
FAS/CD95 AND HIV-1 INDUCED HEMATOPATHOLOGY
批准号:
2871462
负责人:
MORGAN R JENKINS
金额:
$7.56万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-02-01 至 2001-01-31
关键词:
CD95 molecule SCID mouse T cell receptor apoptosis biological signal transduction bone marrow clinical research flow cytometry hematopoiesis human immunodeficiency virus 1 human subject immunoregulation lymphocyte proliferation phenotype polymerase chain reaction tissue /cell culture virus cytopathogenic effect
中文摘要
描述:(改编自申请摘要)细胞凋亡,或
程序性细胞死亡,外周血淋巴细胞已收到
注意HIV-1可能耗尽T淋巴细胞的可能机制。
可以想象,在HIV-1感染的情况下,淋巴细胞的凋亡可能
由几种机制引起,包括CD 4交联,
Fas(APO 1,CD 95)是细胞受体和“死亡信号”的转导子,
和/或上调Fas配体。 更深入地了解
Fas在淋巴细胞中具有非凋亡的调节功能
发展,这表明可能的机制,而不是细胞死亡,
该病毒可产生病理效应。
这项研究的中心假设是,HIV-1可能会改变这种调节,
Fas及其配体在中枢血淋巴器官中的表达,
干扰谱系发育。 使用SCID-hu Thy/Liv和SCID-hu
骨系统作为造血和HIV-1感染模型的实验
将首先研究HIV-1感染对Fas表达的影响,
对造血细胞和淋巴细胞的荧光分选亚群
祖细胞 HIV-1诱导的改变的功能后果
然后使用造血功能测定来研究Fas的表达,
增殖和TCR信号传导。
英文摘要
DESCRIPTION: (Adapted from the application abstract) Apoptosis, or
programmed cell death, of peripheral blood lymphocytes has received
attention as a possible mechanism whereby HIV-1 may deplete T lymphocytes.
Apoptosis of lymphocytes in the setting of HIV-l infection could conceivably
arise by several mechanisms, including CD4 cross-linking, upregulation of
Fas (APO1, CD95) the cellular receptor and transducer of the "death signal",
and/or upregulation of Fas ligand. A deeper understanding of the biology of
Fas has revealed a non-apoptotic, regulatory function for Fas in lymphocyte
development, which suggests possible mechanisms other than cell death by
which virus may exert pathological effects.
The central hypthesis of this study is that HIV-1 may alter the regulation
of Fas and its ligand in central hematolymphoid organs, and thereby
interfere with lineage development. Employing SCID-hu Thy/Liv and SCID-hu
Bone systems as models of hemetopoiesis and of HIV-1 infection, experiments
will first address the effects of HIV-1 infection on the expression of Fas
on fluorescence-sorted subpopulations of hematopoietic and lymphocyte
progenitor cells. The funcitonal consequences of HIV-1-induced alterations
of Fas will then be studied using assays of hematopoietic funciton,
proliferation, and TCR signaling.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1182/blood.v91.8.2672.2672_2672_2678
发表时间:
1998-04-15
期刊:
BLOOD
影响因子:
20.3
作者:
[Jenkins, M, Hanley, MB, McCune, JM]
通讯作者:
McCune, JM
DOI:
10.4049/jimmunol.163.3.1195
发表时间:
1999-08
期刊:
Journal of immunology
影响因子:
4.4
作者:
[M. Jenkins;M. Keir;J. McCune]
通讯作者:
M. Jenkins;M. Keir;J. McCune
FAS/CD95 AND HIV-1 INDUCED HEMATOPATHOLOGY
-
批准号:2002696
-
项目类别:
-
资助金额:$7.56万
-
财政年份:1997
-
负责人:MORGAN R JENKINS
-
依托单位:
FAS/CD95 AND HIV-1 INDUCED HEMATOPATHOLOGY
-
批准号:2653768
-
项目类别:
-
资助金额:$7.56万
-
财政年份:1997
-
负责人:MORGAN R JENKINS
-
依托单位:
海外基金