Heat-shock of normal t-cells and T-cell lines downregulates the TCR/CD3-mediated cytoplasmic Ca2+ responses and the production of inositol trisphosphate.
The application of heat shock to different types of cells is known to cause multiple biochemical and metabolic changes. The predominant event though is an increased synthesis and expression of a family of proteins, the heat-shock proteins (Hsp). Some of these proteins are currently considered to be involved in the signal transduction pathway. We investigated for any possible effects of heating fresh normal peripheral T-cells and T-cell lines, on the early signal transduction events which follow the antigen (Ag) receptor-complex (TCR/CD3) crosslinking. More specifically, the Ag-receptor-initiated free cytoplasmic Ca2+ ([Ca2+]i) responses and the production of inositol 1,4,5-trisphosphate (IP3) were evaluated. Heating fresh unmanipulated peripheral T-cells 8 hours before the TCR/CD3 stimulation resulted in decreased [Ca2+]i responses. This was also true for cells of normal short-term T-cell lines as well. The TCR/CD3-mediated production of IP3, which is a mediator of the [Ca2+]i response, was also decreased in heat-shocked T-cells.
Liossis
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Department of Clinical Physiology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Tsokos
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GC
D000818:Animals; D017252:CD3 Complex / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure
D017252:CD3 Complex; D018840:HSP70 Heat-Shock Proteins; D011948:Receptors, Antigen, T-Cell; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium