Developmental shift in TcR-mediated rescue of thymocytes from glucocorticoid-induced apoptosis

L. Pálinkás, Gergely Talabér, F. Boldizsár, Domokos Bartis, P. Németh, T. Berki

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Glucocorticoid hormone (GC) production by thymic epithelial cells influences TcR signalling in DP thymocytes and modifies their survival. In the present work, we focused on exploring details of GC effects on DP thymocyte apoptosis with or without parallel TcR activation in AND transgenic mice, carrying TcR specific for pigeon cytochrome C, in vivo. Here we show that the glucocorticoid receptor (GR) protein level was the lowest in DP thymocytes, and it was slightly down-regulated by GC analogue, anti-CD3, PCC and combined treatments as well. Exogenous GC analogue treatment or TcR stimulation alone lead to marked DP cell depletion, coupled with a significant increase of early apoptotic cell ratio (AnnexinV staining), marked abrogation of the mitochondrial function in DP cells (CMXRos staining), and significant decrease in the Bcl-2high DP thymocyte numbers, respectively. On the other hand, the simultaneous exposure to these two proapototic signals effectively reversed all the above-described changes. The parallel analysis of CD4 SP cell numbers, AnnexinV, CMXRos, Bcl-2 and GR stainings revealed, that the GR and TcR signals were not antagonistic on the mature thymocytes. These data provide experimental evidence in TcR transgenic mice, in vivo, that when TcR activation and GR signals are present simultaneously, they rescue double positive thymocytes from programmed cell death. The two separate signalling pathways merge in DP thymocytes at such important apoptosis regulating points as the Bcl-2 and GR, showing that their balanced interplay is essential in DP cell survival.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalImmunobiology
Volume213
Issue number1
DOIs
Publication statusPublished - Feb 18 2008

Fingerprint

Thymocytes
Glucocorticoids
Glucocorticoid Receptors
Apoptosis
Hormones
Staining and Labeling
Transgenic Mice
Thymus Hormones
Columbidae
Cytochromes
Cell Survival
Cell Death
Cell Count
Epithelial Cells
Proteins

Keywords

  • Apoptosis
  • Bcl-2
  • Double positive (DP) thymocytes
  • Glucocorticoid hormone (GC)
  • Glucocorticoid receptor (GR)
  • Mutual antagonism

ASJC Scopus subject areas

  • Immunology

Cite this

Developmental shift in TcR-mediated rescue of thymocytes from glucocorticoid-induced apoptosis. / Pálinkás, L.; Talabér, Gergely; Boldizsár, F.; Bartis, Domokos; Németh, P.; Berki, T.

In: Immunobiology, Vol. 213, No. 1, 18.02.2008, p. 39-50.

Research output: Contribution to journalArticle

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