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TID1, a mammalian homologue of the drosophila tumor suppressor lethal(2) tumorous imaginal discs, regulates activation-induced cell death in Th2 cells

Oncogene volume 22, pages 4636–4641 (2003)Cite this article

Abstract

We previously described two human DnaJ proteins, hTid-1L and hTid-1S, which are derived from alternative splicing of the TID1 gene, the human homologue of the Drosophila tumor suppressor lethal(2) tumorous imaginal discs, and showed that hTid-1L promoted while hTid-1S antagonized apoptosis. There are two subsets of helper T cells, Th1 and Th2, of which Th2 cells are significantly less prone to apoptosis induced by stimulation through the T-cell receptor. This apoptotic process is known as activation-induced cell death (AICD). The molecular basis for the differential susceptibility of Th1 and Th2 cells to AICD is not known. Here we show that the antiapoptotic variant, Tid-1S, is selectively induced in murine Th2 cells following activation. Expression of a dominant-negative mutant of hTid-1S in a Th2 cell line strikingly enhanced activation of caspase 3 in response to CD3 stimulation, and caused the cells to become sensitive to AICD. Hence, the accumulation of Tid-1S in Th2 cells following activation represents a novel mechanism that may contribute to the induction of apoptosis resistance during the activation of Th2 cells.

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Acknowledgements

We thank Drs Susanne J Szabo, Estelle Bettelli, Laurie Glimcher, Vijay Kuchroo, Padmini Salgame, and Sara Abramson-Leeman for their generous gifts of T helper cell lines, Dr Hidde Ploegh for his critical comments on the manuscript, John Daniel and other members of the Münger lab for their support and suggestions, and Miranda Grace for excellent technical assistance. We also acknowledge the helpful comments of the anonymous reviewers of this manuscript. This work was supported by a grant from the Collaborative Research Program between Harvard Medical School and Hoechst Marrion Roussel as well as grants from the NIH. JS is a Ryan Fellow, SA was a predoctoral fellow of the Howard Hughes Medical Institute.

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  1. Josh Syken

    Present address: Department of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA

  2. Fernando Macian

    Present address: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

Authors and Affiliations

  1. Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, D2/544A, 02115-5701, MA, USA

    Josh Syken & Karl Münger

  2. Center for Blood Research, Harvard Medical School, Boston, 02115, MA, USA

    Fernando Macian, Suneet Agarwal & Anjana Rao

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Correspondence to Karl Münger.

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Syken, J., Macian, F., Agarwal, S. et al. TID1, a mammalian homologue of the drosophila tumor suppressor lethal(2) tumorous imaginal discs, regulates activation-induced cell death in Th2 cells. Oncogene 22, 4636–4641 (2003). https://doi.org/10.1038/sj.onc.1206569

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