Human T Lymphocyte Clones: Influence of Culture Conditions and Optimization of Proliferative Assays

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Abstract
Many CD4+ human T lymphocyte clones (TLC) are found not to proliferate against appropriate stimulating cells, and many lose this capacity during culture. This may be due, not to a defect in the recognitition of the antigen, but to an inability to produce sufficient amounts of interleukin 2 (IL-2) for autocrine growth, since specific HLA-restricted proliferative responses could be induced in ''non-proliferative'' clones by the addition of exogenous IL-2 or phorbol myristate acetate (PMA). Of various factors tested during expansion procedures of the clones, the proliferative capacity could only be restored by changing the stimulatory cells from B lymphoblastoid cell lines (B-LCL) to peripheral blood mononuclear cells (PBM). The cytotoxicity of the TLC was found to be independent of its proliferative capacity. After restoration of the proliferative capacity, a mouse B lymphoma cell line transfected with the appropriate HLA DQA and DQB genes was still not able to induce proliferation in the absence of exogenous IL-2. We conclude that (1) ''non-proliferative'' TLC may recognize their targets, but fail to proliferative due to temporary lack of IL-2 production, and (2) even ''proliferative'' T cells may fail to respond to certain target cells carrying the specific antigen, such as a murine transfectant, in the absence of exogenous IL-2.