Racial Disparity in gamma/delta T cells

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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.