Role of CD8IL-13 T cells in Chlamydia infection-associated immunopathology

CD8IL-13 T 细胞在衣原体感染相关免疫病理学中的作用

基本信息

  • 批准号:
    9056430
  • 负责人:
  • 金额:
    $ 20.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-08-01 至 2018-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Chlamydia trachomatis genital tract infections have a prevalence of 2-15% in adolescents/young adults in the USA and Europe in spite of public health efforts and effective antibiotic therapy. It is widely accepted that a vaccine is necessary reduce its prevalence. An early C.trachomatis trachoma (eye infection) vaccine delivered poor protection and exacerbated immunopathology. Critical to developing a safe Chlamydia vaccine is a better understanding of immunopathology. Currently there are no practicable biomarkers for Chlamydia immunopathology. In the C. muridarum mouse model others have clearly shown that Chlamydia-specific CD8 T cells are important mediators of immunopathology and infertility. We have recently shown that a subset of Chlamydia-specific CD8 T cell clones derived from mice that self-cleared C. muridarum genital tract infections produce the scar-ogenic cytokines IL-10, TNF�nd IL-13. These CD8 clones are not restricted by MHC class Ia molecules. Similar non-class Ia restricted CD8 T cell clones have been derived from the peripheral blood of humans with C. trachomatis genital tract infections. Using gene expression microarray analysis we have identified a molecular fingerprint for CD8IL-13 T cells. Based on the existing mouse and human Chlamydia literature it clear that the cellular immune response to Chlamydia genital tract infections includes non-class Ia restricted CD8 T cells. The C. muridarum mouse model has unequivocally shown CD8 T cells to be mediators of immunopathology and infertility. We hypothesize that the mechanism underlying CD8 immunopathology is a non-MHC class Ia restricted CD8 T subset secreting IL-10, TNF�and IL-13. To test that hypothesis and investigate the underlying immunobiology we propose the following specific aims: Specific aim #1- to investigate the role of CD8IL-13 T cells in immunopathology utilizing adoptive transfer. We have representative conventional Chlamydia-specific CD8 T cell clones, Chlamydia-specific CD8IL-13 T cell clones, and putative cell surface biomarkers for purifying CD8IL-13 T cells from immune splenocytes or bulk T cell populations. Specific aim #2- to investigate the activation pathway and other immunobiology specific to Chlamydia-specific CD8IL-13 T cells. Utilizing existing T cell clones and gene expression microarray analysis we will compare activated conventional CD8 with activated CD8IL-13 T cells to identify CD8IL-13 specific immunobiology; potentially identifying additional biomarkers and targets for therapeutic intervention. We will als map the epitope source proteins for the Chlamydia-specific CD8 T cell clone panel. Specific aim #3- perform a preliminary investigation of CD8IL-13 T cells in humans. Using putative biomarkers for the CD8IL-13 T cell subset identified in the mouse model we will isolate CD8 T cells from the peripheral blood of healthy individuals and determine whether a similar CD8IL-13 T cell subset exists in humans.
描述(由申请方提供):尽管采取了公共卫生措施和有效的抗生素治疗,但在美国和欧洲,沙眼衣原体生殖道感染在青少年/年轻人中的患病率为2-15%。人们普遍认为,有必要接种疫苗以减少其流行。早期的沙眼衣原体(眼部感染)疫苗提供的保护作用较差,并加剧了免疫病理学。开发安全的衣原体疫苗的关键是更好地了解免疫病理学。目前还没有衣原体免疫病理学的实用生物标志物。在C.其他人已经清楚地表明衣原体特异性CD 8 T细胞是免疫病理学和不育的重要介质。我们最近的研究表明,来自小鼠的衣原体特异性CD 8 T细胞克隆的一个亚群可以自我清除衣原体。鼠生殖道感染产生致瘢痕细胞因子IL-10、TNF和IL-13。这些CD 8克隆不受MHC Ia类分子的限制。类似的非Ia类限制性CD 8 T细胞克隆来源于患有C.沙眼生殖道感染使用基因表达微阵列分析,我们已经确定了CD 8 IL-13 T细胞的分子指纹。基于现有的小鼠和人类衣原体文献,很明显,对衣原体生殖道感染的细胞免疫应答包括非Ia类限制性CD 8 T细胞。梭小鼠模型已经明确显示CD 8 T细胞是免疫病理学和不育的介质。我们推测,CD 8免疫病理学的机制是一个非MHC Ia类限制性CD 8 T亚群分泌IL-10,TNF β和IL-13。为了检验这一假设并研究潜在的免疫生物学,我们提出了以下具体目标:具体目标#1-利用过继转移研究CD 8 IL-13 T细胞在免疫病理学中的作用。我们有代表性的常规衣原体特异性CD 8 T细胞克隆,衣原体特异性CD 8 IL-13 T细胞克隆,和推定的细胞表面生物标志物,用于从免疫脾细胞或大量T细胞群中纯化CD 8 IL-13 T细胞。具体目标#2-研究衣原体特异性CD 8 IL-13 T细胞的活化途径和其他免疫生物学特性。利用现有的T细胞克隆和基因表达微阵列分析,我们将比较活化的常规CD 8与活化的CD 8IL-13 T细胞,以鉴定CD 8IL-13特异性免疫生物学;潜在地鉴定用于治疗干预的其他生物标志物和靶标。我们还将绘制衣原体特异性CD 8 T细胞克隆组的表位源蛋白。具体目标#3-对人体中的CD 8 IL-13 T细胞进行初步研究。使用小鼠模型中鉴定的CD 8 IL-13 T细胞亚群的推定生物标志物,我们将从健康个体的外周血中分离CD 8 T细胞,并确定人类中是否存在类似的CD 8 IL-13 T细胞亚群。

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 }}

RAYMOND Morris JOHNSON其他文献

RAYMOND Morris JOHNSON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('RAYMOND Morris JOHNSON', 18)}}的其他基金

Role of CD8IL-13 T cells in Chlamydia infection-associated immunopathology
CD8IL-13 T 细胞在衣原体感染相关免疫病理学中的作用
  • 批准号:
    8805282
  • 财政年份:
    2015
  • 资助金额:
    $ 20.92万
  • 项目类别:
Six new Chlamydia epitopes
六个新的衣原体表位
  • 批准号:
    8426077
  • 财政年份:
    2012
  • 资助金额:
    $ 20.92万
  • 项目类别:
Six new Chlamydia epitopes
六个新的衣原体表位
  • 批准号:
    8280847
  • 财政年份:
    2012
  • 资助金额:
    $ 20.92万
  • 项目类别:
Cellular Immunity to Chlamydua at the Epithelial Interface
上皮界面对衣原体的细胞免疫
  • 批准号:
    7900101
  • 财政年份:
    2009
  • 资助金额:
    $ 20.92万
  • 项目类别:
Cellular Immunity to Chlamydua at the Epithelial Interface
上皮界面对衣原体的细胞免疫
  • 批准号:
    7458802
  • 财政年份:
    2007
  • 资助金额:
    $ 20.92万
  • 项目类别:
Cellular Immunity to Chlamydua at the Epithelial Interface
上皮界面对衣原体的细胞免疫
  • 批准号:
    7640641
  • 财政年份:
    2007
  • 资助金额:
    $ 20.92万
  • 项目类别:
Cellular Immunity to Chlamydua at the Epithelial Interface
上皮界面对衣原体的细胞免疫
  • 批准号:
    7318666
  • 财政年份:
    2007
  • 资助金额:
    $ 20.92万
  • 项目类别:
Cellular Immunity to Chlamydua at the Epithelial Interface
上皮界面对衣原体的细胞免疫
  • 批准号:
    7883271
  • 财政年份:
    2007
  • 资助金额:
    $ 20.92万
  • 项目类别:
Immunobiology of Chlamydia
衣原体免疫生物学
  • 批准号:
    6736342
  • 财政年份:
    2002
  • 资助金额:
    $ 20.92万
  • 项目类别:
Immunobiology of Chlamydia
衣原体免疫生物学
  • 批准号:
    6647227
  • 财政年份:
    2002
  • 资助金额:
    $ 20.92万
  • 项目类别:

相似海外基金

Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The impact of changes in social determinants of health on adolescent and young adult mental health during the COVID-19 pandemic: A longitudinal study of the Asenze cohort in South Africa
COVID-19 大流行期间健康社会决定因素的变化对青少年和年轻人心理健康的影响:南非 Asenze 队列的纵向研究
  • 批准号:
    10755168
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
A Priority Setting Partnership to Establish a Patient, Caregiver, and Clinician-identified Research Agenda for Adolescent and Young Adult Cancer in Canada
建立优先合作伙伴关系,以建立患者、护理人员和临床医生确定的加拿大青少年和年轻人癌症研究议程
  • 批准号:
    480840
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
    Miscellaneous Programs
Incidence and Time on Onset of Cardiovascular Risk Factors and Cardiovascular Disease in Adult Survivors of Adolescent and Young Adult Cancer and Association with Exercise
青少年和青年癌症成年幸存者心血管危险因素和心血管疾病的发病率和时间以及与运动的关系
  • 批准号:
    10678157
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
Fertility experiences among ethnically diverse adolescent and young adult cancer survivors: A population-based study
不同种族青少年和年轻成年癌症幸存者的生育经历:一项基于人群的研究
  • 批准号:
    10744412
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
Treatment development for refractory leukemia using childhood/adolescent, and young adult leukemia biobank
利用儿童/青少年和青年白血病生物库开发难治性白血病的治疗方法
  • 批准号:
    23K07305
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular design of Two-Way Player CAR-T cells to overcome disease/antigen heterogeneity of childhood, adolescent, and young adult cancers
双向 CAR-T 细胞的分子设计,以克服儿童、青少年和年轻成人癌症的疾病/抗原异质性
  • 批准号:
    23H02874
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Using Tailored mHealth Strategies to Promote Weight Management among Adolescent and Young Adult Cancer Survivors
使用量身定制的移动健康策略促进青少年和年轻癌症幸存者的体重管理
  • 批准号:
    10650648
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
Developing and Testing a Culturally Tailored Mobile Health and Social MediaPhysical Activity Intervention Among Adolescent and Young Adult ChildhoodCancer Survivors
开发和测试针对青少年和青年儿童癌症幸存者的文化定制移动健康和社交媒体体育活动干预
  • 批准号:
    10736526
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
Pilot Project 1: Creating Bridges to Reproductive Health Care for Rural Adolescent and Young Adult Cancer Survivors
试点项目 1:为农村青少年和青年癌症幸存者搭建生殖保健桥梁
  • 批准号:
    10762146
  • 财政年份:
    2023
  • 资助金额:
    $ 20.92万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了