HEAT-STRESSED CD4-LYMPHOCYTES - DIFFERENTIAL MODULATIONS OF ADHESIVENESS TO EXTRACELLULAR-MATRIX GLYCOPROTEINS, PROLIFERATIVE RESPONSES ANDTUMOR-NECROSIS-FACTOR-ALPHA SECRETION( T)

Although cells of the immune system often function under feverish cond itions, the effects of elevated temperatures on T cells have not been fully elucidated. Herein, the effects of a 1-hr exposure to 41-degrees of CD4+ human T cell were studied. Heat-shock treatment of activated CD4+ T cells reduced their adhesion to fibronectin and laminin, the ma jor adhesive glycoproteins of the extracellular matrix (ECM) by 25-40% . This decrease was partially due to a minor decrease in the surface e xpression of beta1 integrins, which specifically interact with fibrone ctin and laminin. In contrast, the capacities of heat-stressed T cells to proliferate and to secrete tumour necrosis factor-alpha (TNF-alpha ) were increased upon cell activation. In vivo, heat-treated antigen-p rimed murine T cells, injected directly into the antigen challenging s ite, induced a more severe delayed-type hypersensitivity (DTH) respons e than those not exposed to elevated temperatures. In contrast, the sa me heat-treated cells inoculated intravenously did not induce DTH, sug gesting that these cells were impaired with respect to penetration of blood vessel walls. Thus, the effects of heat shock on key cellular fu nctions are expressed in different manners: T-cell-ECM adhesiveness an d subsequent extravasation are impaired, whereas their abilities to pr oliferate and to secrete TNF-alpha are augmented.