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

Abstract 1. 1. Human T cell proliferation is suppressed at 27°C, and is both diminished and delayed at 32°C. 2. 2. Temperature shift-up and viability assays indicated that concanavalin A stimulation at 27°C induced cell death in contrast to a transient unresponsiveness (anergy) induced by monoclonal anti-CD3 antibody (αCD3) and the superantigen, staphylococcal exterotoxin B. 3. 3. Phytohemagglutinin also induced cell death at 27°C; however, some cells remained viable and proliferation occurred when such cultures were subsequently moved to 37°C. 4. 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°C was required to bypass the block at 27°C. 5. 5. With the exception of αCD3, stimulation at 27°C with the mitogens resulted in interleukin-2 secretion, indicating that the low temperature block(s) is a relatively late event in cell activation.