Heat-stressed CD4+ T lymphocytes: differential modulations of adhesiveness to extracellular matrix glycoproteins, proliferative responses and tumour necrosis factor-alpha secretion.
Although cells of the immune system often function under feverish conditions, 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 major adhesive glycoproteins of the extracellular matrix (ECM) by 25-40%. This decrease was partially due to a minor decrease in the surface expression of beta 1 integrins, which specifically interact with fibronectin 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-primed murine T cells, injected directly into the antigen challenging site, induced a more severe delayed-type hypersensitivity (DTH) response than those not exposed to elevated temperatures. In contrast, the same heat-treated cells inoculated intravenously did not induce DTH, suggesting that these cells were impaired with respect to penetration of blood vessel walls. Thus, the effects of heat shock on key cellular functions are expressed in different manners: T-cell-ECM adhesiveness and subsequent extravasation are impaired, whereas their abilities to proliferate and to secrete TNF-alpha are augmented.
Hershkoviz
R
R
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Alon
R
R
Mekori
Y A
YA
Gilat
D
D
Cahalon
L
L
Miller
A
A
Lider
O
O
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D014409:Tumor Necrosis Factor-alpha