Racial Disparity in gamma/delta T cells

描述(由申请人提供)：T淋巴细胞亚群的区别在于T细胞受体的伽马/德尔塔形式的表达以及包括CD4和CD8在内的谱系标志的缺失。这些伽马/德尔塔T细胞识别非传统抗原，包括甾醇合成的中间产物戊基焦磷酸，并对许多人类肿瘤具有细胞毒性。Vg2Vd2+亚群的急剧丢失是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，Vg2Vd2 T细胞的丧失将剥夺免疫系统产生干扰素-伽马的重要来源，并减少B细胞的同型转换，这是产生病毒中和抗体的必要机制。对Vg2Vd2 T细胞的研究针对HIV/AIDS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丧失以及抗逆转录病毒治疗的影响。 回顾了我们自己关于健康对照中Vg2Vd2 T细胞的大量数据库，以及其他进行过这类工作的人的个人交流，发现公布的正常值完全来自高加索人。这一认识引起了人们的担忧，即我们现有的正常值并不是来自适合研究非裔美国人艾滋病毒/艾滋病的对照组。此外，我们发现在接受检查的最初的非裔美国人捐赠者中，Vg2Vd2 T细胞水平和功能异常低。这些考虑，加上其他关于非洲人群中伽马/德尔塔T细胞的初步和已发表的数据，强烈鼓励我们测试种族/民族对Vg2Vd2 T细胞水平、功能和谱系的可能影响。 这个R03应用程序解决了对伽马/增量T细胞研究的对照组的重新评估。我们将收集和鉴定25名居住在巴尔的摩的健康成年非裔美国人和25名高加索人的样本，以测试基于种族/民族的可能偏见。在第二项研究中，我们对非裔美国人和白人母亲分娩的脐带血伽马/德尔塔T细胞进行了类似的分析。这些研究将表明，目前的健康对照数据是否适合在巴尔的摩进行研究，那里的HIV+人口绝大多数是非裔美国人(马里兰大学诊所的87%)。 公共卫生相关性：人类淋巴细胞的一个亚群被称为伽马/德尔塔T细胞，已被广泛研究为艾滋病毒感染、疾病和治疗影响的生物标记物。直到最近，健康人的正常对照数据仅来自对艾滋病毒阴性的高加索人的研究。我们在前两名非裔美国人捐献者中观察到异常低的伽马/德尔塔T细胞，并决定通过比较生活在巴尔的摩的高加索人和非裔美国人的伽马/德尔塔T细胞来重新评估我们的控制值。通过将健康的成年非裔美国人纳入研究组，我们确保控制组与主导当地艾滋病毒+社区的以非裔美国人为主的人口相匹配。

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.