Human Lymphocyte Function in Air or at Physiologic O2

Stanford University, Stanford CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Physiologic oxygen concentrations in normal lymphoid tissues and at sites of lymphoid development typically range from four to seven percent. However, lymphocytes are almost universally cultured in 20 percent oxygen, i.e., in incubators that adjust the carbon dioxide levels but are otherwise equilibrated with air. In essence, this means that virtually all ex vivo studies with human lymphocytes have been conducted with cells cultured at 2-5 times their physiologic oxygen levels. The significance of this disparity is largely unexplored, although several reports indicate that the oxygen levels at which lymphocytes are cultured influence aspects of commonly studied functions and that culturing at physiologic oxygen levels could be key to the clinical success of ex vivo lymphocyte treatments protocols (e.g., expansion of Tumor Infiltrating Lymphocytes for cancer treatment and expansion of CD4 T cells for HIV treatment). Studies proposed here are designed to determine the functional impact of culturing lymphocytes in excess oxygen and to determine whether effects that are detected can be overcome by culturing at low oxygen levels or inclusion of antioxidants in the culture medium. [unreadable] [unreadable] [unreadable]