EXPRESSION OF BCL 2 IN SIV INFECTED THYMIC TISSUE
BCL 2 在 SIV 感染的胸腺组织中的表达
基本信息
- 批准号:6591316
- 负责人:
- 金额:$ 11.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-05-01 至 2003-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Cell death due to apoptosis plays a critical role in the
development of T cells in the thymus Several intracellular molecular
mechanisms have been identified that regulate apoptosis in thymocytes,
including bcl-2, bcl-x, bax, R-ras and fas Retroviral infection of the
thymus with HIV-1 or SIV results in selective thymocyte depletion, and
apoptosis has been shown to contribute to this increase in cell death
The precise mechanism whereby lentiviruses induce apoptosis remains
controversial Using a novel system of in vitro T cell differentiation,
we developed a multiparameter flow cytometry assay to determine the
role of fas, fas-ligand and bcl-2 in apoptosis of thymocytes as a
result of SIV infection We detected a 3-fold increase of apoptosis
(detected by Tdt staining) in in vitro cultures 48 post infection with
SIV239 Furthermore, the increase in Tdt+ cells is accompanied by a
decrease in bcl-2 (2- 3-fold) expression and an increase in surface
fas expressio n (4-5 fo ld) as determined by flow cytometry Fas ligand
was found to be increased in single positive thymocytes in vivo, but
not in the in vitro culture system This data clearly demonstrates that
both the bcl-2 and fas pathways are involved in SIV induced apoptosis
of thymocytes and that lentiviral infection leads to thymocyte
apoptosis Using FACS we demonstrated that SIV infection results in an
initial 15-20% decrease of surface fas expression in CD4+CD8+ and
CD4+CD8- cells, and not CD4-CD8+ cells However, by day 7
post-infection, we observed a profound reversal of this phenomenon,
with a dramatic increase (6 fold) in fas expression in CD4+CD8+ and
CD4+CD8- cells, as compared to uninfected cultures These studies have
been extended to examine the effects of acute SIV-infection in vivo,
with respect to alterations in the thymus Data from these studies
demonstrated that the surface levels of fas on thymocytes from normal
neonates is generally low (1-3% of all cells), and does not
demonstrate any specific phenotypic distribution After SIV infection
the level of surface fas changes modestly, increasing to a maximum of
8% of thymocytes of d14 post-infection This was not accompanied by any
significant alteration in surface expression of fas-ligand This
observation was in contrast to the fluctuations in bcl-2 levels
Uninfected neonatal thymocytes express large amounts of bcl-2,
consistent with the observations of others However, rapidly during the
course of SIV infection the number of bcl-2 positive cells decreases,
as well as the amount of bcl-2 per cell as detected by flow cytometry
The lowest levels of bcl-2 occur coincident with the largest amount of
apoptosis, detected by Tdt staining By day 21 of acute SIV infection,
the levels of virus begin to decline and this is associated with the
resumption of normal thymic function Specifically, by d21, the number
of apoptotic cells is drastically reduced, and the number of bcl-2
cells begins to approach baseline levels The level of bcl-2 on a per
cell basis recovers only by day 50 post-infection Based on these
observations, it would appear that dysregulation of the bcl-2 pathway
is the predominant mechanism associated with the apoptosis that
accompanies retroviral infection of the thymus REFERENCES Wykrzykowska
JJ, Rosenzweig M, Veazey RS, Simon MA, Halvorsen K, Desrosiers RC,
Johnson RP, Lackner AA Early regeneration of thymic progenitors in
rhesus macaques infected with simian immunodeficiency virus J Exp Med
1998, 187:1767-1778 Gardner JP, Rosenzweig M*, Marks DF, Harper D,
Gaynor K, Fallon RJ, Wall DA, Johnson RP, Scadden DT T lymphopoietic
capacity of cord blood-derived CD34+ progenitor cells Exp Hematol
1998; 26:991-999
细胞凋亡导致的细胞死亡在细胞凋亡过程中起关键作用
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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M ROSENZWEIG其他文献
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{{ truncateString('M ROSENZWEIG', 18)}}的其他基金
STEM CELL GENE THERAPY USING LONG TERM BONE MARROW CULTURE TRANSDUCTION PROTOCOL
使用长期骨髓培养转导方案的干细胞基因治疗
- 批准号:
6591288 - 财政年份:2002
- 资助金额:
$ 11.11万 - 项目类别:
IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES
恒河猴 T 细胞更新的体内分析
- 批准号:
6591317 - 财政年份:2002
- 资助金额:
$ 11.11万 - 项目类别:
FLT LIGAND PERIPHERAL BLOOD STEM CELL MOBILIZATION FOR STEM CELL GENE THERAPY
用于干细胞基因治疗的 FLT 配体外周血干细胞动员
- 批准号:
6591324 - 财政年份:2002
- 资助金额:
$ 11.11万 - 项目类别:
XENOGENEIC THYMIC TRANSPLANTATION AS AN ADJUNCT TO TREATMENT OF AIDS
异种胸腺移植作为艾滋病治疗的辅助手段
- 批准号:
6591306 - 财政年份:2002
- 资助金额:
$ 11.11万 - 项目类别:
EXPRESSION OF BCL 2 IN SIV INFECTED THYMIC TISSUE
BCL 2 在 SIV 感染的胸腺组织中的表达
- 批准号:
6453762 - 财政年份:2001
- 资助金额:
$ 11.11万 - 项目类别:
IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES
恒河猴 T 细胞更新的体内分析
- 批准号:
6453763 - 财政年份:2001
- 资助金额:
$ 11.11万 - 项目类别:
STEM CELL GENE THERAPY USING LONG TERM BONE MARROW CULTURE TRANSDUCTION PROTOCOL
使用长期骨髓培养转导方案的干细胞基因治疗
- 批准号:
6453734 - 财政年份:2001
- 资助金额:
$ 11.11万 - 项目类别:
FLT LIGAND PERIPHERAL BLOOD STEM CELL MOBILIZATION FOR STEM CELL GENE THERAPY
用于干细胞基因治疗的 FLT 配体外周血干细胞动员
- 批准号:
6453770 - 财政年份:2001
- 资助金额:
$ 11.11万 - 项目类别:
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