Heat stress downregulates TCR zeta chain expression in human T lymphocytes

After heat treatment, human T lymphocytes downregulate the T-cell receptor (TCR)/CD3-mediaied (Ca2+](i) response and production of inositol triphospha te. Here we demonstrate that heat treatment of T lymphocytes at sublethal t emperature decreases the expression of TCR zeta chain, which plays a critic al role in the regulation of TCR/CD3-mediated signal transduction. Downregu lation of TCR i chain in heat-treated T cells was observed at 8 h and reach ed a maximum at 16 h. Under these conditions, the expression of CD3 is an e lement of or TCR alpha beta chains was minimally affected. Consistent with the decrease in TCR zeta chain, a reduction in the level of TCR/CD3 induced tyrosine phosphorylation of several cellular protein substrates, and a del ay in the kinetics of peak tyrosine phosphorylation was observed in heat-tr eated T cells, interestingly, analysis of the TCR i chain content in the de tergent-insoluble membrane fraction showed that heat treatment induces tran slocation of soluble TCR zeta chain to the cell membranes. In addition, the mRNA level of TCR zeta; chain was reduced in heat-treated T cells. Correla tive with the downregulation of TCR zeta; chain mRNA, the level of the TCR zeta chain transcription factor Elf-1 was also reduced in heat-treated cell s. We conclude that heat stress causes a decrease in the level of TCR zeta chain by increasing its association with the membranes and decreasing the t ranscription of the TCR zeta gene. Decreased expression of the TCR zeta cha in is apparently responsible for the decreased TCR/CD3 responses of T cells , (C) 2000 Wiley-Liss, Inc.