Anergy or cell death induced by low physiological temperature in mitogen-stimulated human T lymphocytes

1. Human T cell proliferation is suppressed at 27 degrees C, and is both diminished and delayed at 32 degrees C. 2. Temperature shift-up and viability assays indicated that concanavalin A stimulation at 27 degrees C induced cell death in contrast to a transient unresponsiveness (anergy) induced by monoclonal anti-CD3 antibody (alpha CD3) and the superantigen, staphylococcal exterotoxin B. 3. Phytohemagglutinin also induced cell death at 27 degrees C; however, some cells remained viable and proliferation occurred when such cultures were subsequently moved to 37 degrees C. 4. Low temperature suppression of T cell activation was not overcome by a mixture of phorbol ester and calcium ionophore indicating a probable block post-protein kinase C activation. This was confirmed in temperature shift-down assays where incubation for 18-24 h at 37 degrees C was required to bypass the block at 27 degrees C. 5. With the exception of alpha CD3, stimulation at 27 degrees C With the mitogens resulted in interleukin-2 secretion, indicating that the low temperature block(s) is a relatively late event in cell activation. Copyright (C) 1996 Elsevier Science Ltd.