Racial Disparity in gamma/delta T cells
γ/δ T 细胞的种族差异
基本信息
- 批准号:7492579
- 负责人:
- 金额:$ 7.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-03-15 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:AIDS related cancerAIDS/HIV problemAddressAdultAfricanAfrican AmericanAgeAntigensB-LymphocytesBaltimoreBiological MarkersCD8-Positive T-LymphocytesCD8B1 geneCameroonCaucasiansCaucasoid RaceCell CountChildClinicCommunitiesControl GroupsControlled StudyDataDatabasesDiseaseDisease ProgressionEnsureEthnic OriginEvaluationFemaleFundingFutureHIVHIV InfectionsHighly Active Antiretroviral TherapyHumanImmune systemImmunityImmunoglobulin Class SwitchingIn VitroIndividualInfectionInterferon Type IILifeLinkLymphocyteMacacaMarylandMinorMothersMusNatural HistoryNigeriaNormal RangeNumbersPatternPersonal CommunicationPersonsPopulationProcessPublic HealthPublishingRaceRangeRateSIVSourceSpecimenSterolsT-Cell ReceptorT-LymphocyteT-Lymphocyte SubsetsTestingTumor ImmunityUmbilical Cord BloodUniversitiesVirusVirus DiseasesWorkantiretroviral therapybasecytotoxicdesignfunctional lossinterestmaleneutralizing antibodyprogramsracial differenceresearch studyresponsesecondary infectionstemtumor
项目摘要
DESCRIPTION (provided by applicant): A subset of T lymphocytes is distinguished by expression of the gamma/delta form of T cell receptor and the absence of lineage markers including CD4 and CD8. These gamma/delta T cells recognize unconventional antigens including prenylpyrophosphate intermediates of sterol synthesis, and are cytotoxic for a number of human tumors. Precipitous loss of the Vg2Vd2+ subset is a biomarker for HIV infection and disease progression. Based on mouse studies and in vitro experiments, the loss of Vg2Vd2 T cells will deprive the immune system of an important source for interferon-gamma and reduce isotype class switching by B cells, a necessary mechanism for producing virus neutralizing antibodies. Studies on Vg2Vd2 T cells target multiple aspects of HIV/AIDS, including the mechanisms for disease progression, the loss of tumor immunity leading to AIDS-related malignancies and the impact of antiretroviral therapy.
A review of our own substantial data base on Vg2Vd2 T cells in healthy control, along with personal communications from others who have conducted this type of work, revealed that published normal values were derived exclusively from Caucasians. This realization raised concerns that our existing normal values were not derived from control groups that are appropriate for studies of HIV/AIDS in African Americans. Further, we found abnormally low Vg2Vd2 T cell levels and function in the initial African American donors that were examined. These considerations, along with other preliminary and published data on gamma/delta T cells in African populations, strongly encouraged us to test for a possible effect of race/ethnicity on Vg2Vd2 T cell levels, function and repertoire.
This RO3 application addresses the re-evaluation of control groups for gamma/delta T cell studies. We will accumulate and characterize specimens from 25 healthy adult African Americans and 25 Caucasians living in Baltimore, to test for possible bias based on race/ethnicity. In a second study, we perform similar analyses on cord blood gamma/delta T cells from deliveries to African American versus Caucasian mothers. These studies will show whether the current data for healthy controls is appropriate for studies in Baltimore, where the HIV+ population is overwhelmingly African American (87% in the University of Maryland clinics).
PUBLIC HEALTH RELEVANCE: A subset of human lymphocytes designated gamma/delta T cells, has been studies extensively as a biomarker for HIV infection, disease and the impact of therapy. Until recently, the normal control data for healthy individuals was derived exclusively from studies on HIV-negative Caucasians. We observed abnormally low gamma/delta T cells in the first two African American donors and decided to re-evaluate our control values, by comparing gamma/delta T cells in Caucasian versus African Americans living in Baltimore. By including healthy, adult African Americans in the study group, we are ensuring that the control group matches the predominantly African American population that dominates the local HIV+ community.
描述(由申请人提供):T淋巴细胞亚群的特征在于表达T细胞受体的γ/δ形式,并且不存在包括CD 4和CD 8在内的谱系标志物。这些γ/δ T细胞识别非常规抗原,包括甾醇合成的异戊烯焦磷酸中间体,并且对许多人类肿瘤具有细胞毒性。Vg 2 Vd 2+亚群的大量丢失是HIV感染和疾病进展的生物标志物。基于小鼠研究和体外实验,Vg 2 Vd 2 T细胞的损失将剥夺免疫系统的干扰素-γ的重要来源,并减少B细胞的同种型类别转换,这是产生病毒中和抗体的必要机制。对Vg 2 Vd 2 T细胞的研究针对艾滋病毒/艾滋病的多个方面,包括疾病进展的机制,导致艾滋病相关恶性肿瘤的肿瘤免疫力丧失以及抗逆转录病毒治疗的影响。
对我们自己的关于健康对照中Vg 2 Vd 2 T细胞的大量数据库的回顾,沿着进行这类工作的其他人的个人通信,揭示了发表的正常值仅来自高加索人。这一认识引起了人们的关注,即我们现有的正常值不是来自于适合于非裔美国人艾滋病毒/艾滋病研究的对照组。此外,我们发现异常低的Vg 2 Vd 2 T细胞水平和功能在最初的非洲裔美国人的捐助者进行了检查。这些考虑因素,沿着其他关于非洲人群中γ/δ T细胞的初步和已发表的数据,强烈鼓励我们测试人种/种族对Vg 2 Vd 2 T细胞水平、功能和库的可能影响。
该RO 3申请涉及γ/δ T细胞研究对照组的重新评价。我们将收集并表征来自居住在巴尔的摩的25名健康成年非裔美国人和25名高加索人的标本,以检测基于人种/种族的可能偏倚。在第二项研究中,我们对非裔美国人与白人母亲分娩的脐带血γ/δ T细胞进行了类似的分析。这些研究将显示健康对照的当前数据是否适用于巴尔的摩的研究,那里的艾滋病毒阳性人群绝大多数是非洲裔美国人(马里兰州大学诊所的比例为87%)。
公共卫生关系:人类淋巴细胞的一个亚群称为γ/δ T细胞,已被广泛研究作为HIV感染,疾病和治疗影响的生物标志物。直到最近,健康个体的正常对照数据仅来自HIV阴性高加索人的研究。我们在前两名非洲裔美国人供体中观察到异常低的γ/δ T细胞,并决定通过比较居住在巴尔的摩的高加索人与非洲裔美国人的γ/δ T细胞来重新评估我们的对照值。通过将健康的成年非洲裔美国人纳入研究组,我们确保对照组与当地艾滋病毒阳性社区占主导地位的主要非洲裔美国人人口相匹配。
项目成果
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C. David Pauza其他文献
C. David Pauza的其他文献
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{{ truncateString('C. David Pauza', 18)}}的其他基金
T-follicular helper cells in Env-immunized macaques
Env 免疫猕猴中的滤泡辅助 T 细胞
- 批准号:
8262539 - 财政年份:2012
- 资助金额:
$ 7.5万 - 项目类别:
Synthetic Variable Domain Glycopeptides for Neutralizing Epitope Characterization
用于中和表位表征的合成可变结构域糖肽
- 批准号:
8505372 - 财政年份:2012
- 资助金额:
$ 7.5万 - 项目类别:
T-follicular helper cells in Env-immunized macaques
Env 免疫猕猴中的滤泡辅助 T 细胞
- 批准号:
8515924 - 财政年份:2012
- 资助金额:
$ 7.5万 - 项目类别: