ANERGY, APOPTOSIS AND CD28 IN CD8+ T CELLS DURING AIDS

艾滋病期间 CD8 T 细胞的无能、凋亡和 CD28

基本信息

  • 批准号:
    2672388
  • 负责人:
  • 金额:
    $ 23.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1995
  • 资助国家:
    美国
  • 起止时间:
    1995-07-01 至 2000-06-30
  • 项目状态:
    已结题

项目摘要

CD8+ T cells in human immunodeficiency virus (HIV)-infected people undergo significant alterations in phenotype and function during the disease. There is chronic activation as indicated by an increase in the expression of activation antigens such as CD38, DR, and CD57. The development of preactivated major histocompatibility complex (MHC)-restricted, HIV- specific cytotoxic T lymphocyte also is a unique feature of infection. The CD8+ T cells also are anergic and apoptotic in vitro and have reduced cloning efficiency. Late in infection, HIV-specific CTL function is lost which may be responsible for HIV disease progression. Our hypothesis is that many of these observations are related directly to the loss of surface expression of the important T cell activation molecule, CD28. The interaction of CD28 with ligands on antigen-presenting cells is known to be crucial for T cell activation. We propose to address the importance of CD28 function in HIV infection by three specific aims. Specific Aim 1 is to perform a cross-sectional study of HIV+ people early after infection, during the asymptomatic period, in patients with AIDS, and in long-term survivors. We will determine the timing of CD28 loss on CD8+ T cells as a function of disease status, immune function, virologic status, and susceptibility of cells to apoptosis. These studies will determine the clinical significance of our observation and will ask whether the CD8 cells are affected early in infection or whether intact CD28 expression in a determinant of long-term survival. Specific Aim 2 is to perform a longitudinal study to address whether the loss of HIV-specific CTL function late in infection is due to loss of CD28 expression, associated with viremia, development of anergy, apoptosis, and clinical progression. This study addresses whether loss of containment of HIV by cytotoxic T cells is due to loss of CD28 expression. Specific Aim 3 examines a specific mechanism of CD28 gene regulation. A major hypothesis of HIV pathogenesis is that a T-1 to T-2 switch occurs in cytokine production as the disease progresses. No one has addressed the ramifications of the hypothesis on development of CD8+ T cells or their function. Preliminary data indicate that a T-2 cytokine environment causes CD28 down-regulation on CD8+ T cells from control individuals. We propose to test the hypothesis that CD28 gene transcription is negatively regulated by T-2 cytokines via a reduction in NF-kB activity. Thus, these studies will explore the molecular regulation of CD28 expression. This proposal has significance for vaccine design and gene therapy approaches because understanding the role of CD28 in containment of HIV by CD8+ T cells may lead to augmentation or intervention.
CD8+ T细胞在人类免疫缺陷病毒(HIV)感染的人群中经历

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

DOROTHY E. LEWIS其他文献

DOROTHY E. LEWIS的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('DOROTHY E. LEWIS', 18)}}的其他基金

Immonology Core
免疫学核心
  • 批准号:
    7929993
  • 财政年份:
    2010
  • 资助金额:
    $ 23.96万
  • 项目类别:
Immunology Core
免疫学核心
  • 批准号:
    7683338
  • 财政年份:
    2008
  • 资助金额:
    $ 23.96万
  • 项目类别:
Flow Cytometry Resource
流式细胞术资源
  • 批准号:
    7514635
  • 财政年份:
    2007
  • 资助金额:
    $ 23.96万
  • 项目类别:
Molecular Nature of Fetal DNA in Maternal Plasma
母体血浆中胎儿 DNA 的分子性质
  • 批准号:
    7330493
  • 财政年份:
    2004
  • 资助金额:
    $ 23.96万
  • 项目类别:
Formation and Function of Human CD28-Negative T Cells
人 CD28 阴性 T 细胞的形成和功能
  • 批准号:
    6695343
  • 财政年份:
    2003
  • 资助金额:
    $ 23.96万
  • 项目类别:
Formation and Function of Human CD28-Negative T Cells
人 CD28 阴性 T 细胞的形成和功能
  • 批准号:
    6785382
  • 财政年份:
    2003
  • 资助金额:
    $ 23.96万
  • 项目类别:
CORE--IMMUNOLOGY FACILITY
核心--免疫学设施
  • 批准号:
    6665548
  • 财政年份:
    2002
  • 资助金额:
    $ 23.96万
  • 项目类别:
CORE--IMMUNOLOGY FACILITY
核心——免疫设施
  • 批准号:
    6506206
  • 财政年份:
    2001
  • 资助金额:
    $ 23.96万
  • 项目类别:
CORE--IMMUNOLOGY FACILITY
核心——免疫设施
  • 批准号:
    6355552
  • 财政年份:
    2000
  • 资助金额:
    $ 23.96万
  • 项目类别:
CORE--IMMUNOLOGY FACILITY
核心——免疫设施
  • 批准号:
    6201210
  • 财政年份:
    1999
  • 资助金额:
    $ 23.96万
  • 项目类别:

相似海外基金

FUNCTION OF THE CD28 MOLECULE
CD28 分子的功能
  • 批准号:
    2182536
  • 财政年份:
    1992
  • 资助金额:
    $ 23.96万
  • 项目类别:
FUNCTION OF THE HUMAN CD28 MOLECULE
人类 CD28 分子的功能
  • 批准号:
    3303619
  • 财政年份:
    1992
  • 资助金额:
    $ 23.96万
  • 项目类别:
FUNCTION OF THE CD28 MOLECULE
CD28 分子的功能
  • 批准号:
    2182535
  • 财政年份:
    1992
  • 资助金额:
    $ 23.96万
  • 项目类别:
FUNCTION OF THE HUMAN CD28 MOLECULE
人类 CD28 分子的功能
  • 批准号:
    3303618
  • 财政年份:
    1992
  • 资助金额:
    $ 23.96万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了