CD30 mediates thymic Programmed Cell Death (PCD) through a BCL-2 sensitive pathway

R. Chiarle, Antonello Podda, G. Prolla, E. R. Podack, G. J. Thorbecke, G. Inghirami

Research output: Contribution to journalArticle

Abstract

The CD30 molecule is a TNF-R member, whose function in normal and neoplastic lymphocytes is still largely unknown. To study the role of CD30 on T cells, transgenic mice were generated using the complete open reading frame of murine CD30 (1.6 kb) under the transcriptional control of the minimal murine CD4 promoter (487 bp), containing the transcription initiation site and 70 bp of the untranslated first exon, and the minimal CD4 enhancer (339 bp). Multiple lines of mice were obtained in which high surface CD30 expression was restricted to T cells in all different stages of differentiation. The mice had normal thymic maturation, but a decreased number of peripheral T cells in secondary lymphoid organs. The CD30 overexpression did not alter the thymocyte PCD, induced by radiation, dexamethasone, ionomycin, PMA and activation via Fas or CD3, but it allowed PCD with CD30 cross-linking by anti-CD30 or CD30L. It also enhanced PCD induced via CD3 + CD30 co-stimulation. CD30 induced PCD was blocked by caspase 1 and caspase 3 inhibitors (Z-YVAD-cmk and Z-DEVD-fmk). CD30 induced PCD did not influence NFκB protein or Fas, Flice, Fadd, Flip, Tradd, Traf-1 and 2 mRNA levels. However, anti-CD30 induced PCD was totally blocked by simultaneous BCL-2 overexpression. These results demonstrate that CD30 is an important effector of thymic PCD.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

Fingerprint

Cell death
Cell Death
apoptosis
T-cells
mice
T-lymphocytes
T-Lymphocytes
caspase-1
Caspase 1
Ionomycin
Caspase Inhibitors
thymocytes
Lymphocytes
Transcription Initiation Site
caspase-3
Thymocytes
dexamethasone
crosslinking
Caspase 3
Dexamethasone

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Chiarle, R., Podda, A., Prolla, G., Podack, E. R., Thorbecke, G. J., & Inghirami, G. (1998). CD30 mediates thymic Programmed Cell Death (PCD) through a BCL-2 sensitive pathway. FASEB Journal, 12(5).

CD30 mediates thymic Programmed Cell Death (PCD) through a BCL-2 sensitive pathway. / Chiarle, R.; Podda, Antonello; Prolla, G.; Podack, E. R.; Thorbecke, G. J.; Inghirami, G.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

Chiarle, R, Podda, A, Prolla, G, Podack, ER, Thorbecke, GJ & Inghirami, G 1998, 'CD30 mediates thymic Programmed Cell Death (PCD) through a BCL-2 sensitive pathway', FASEB Journal, vol. 12, no. 5.
Chiarle R, Podda A, Prolla G, Podack ER, Thorbecke GJ, Inghirami G. CD30 mediates thymic Programmed Cell Death (PCD) through a BCL-2 sensitive pathway. FASEB Journal. 1998 Mar 20;12(5).
Chiarle, R. ; Podda, Antonello ; Prolla, G. ; Podack, E. R. ; Thorbecke, G. J. ; Inghirami, G. / CD30 mediates thymic Programmed Cell Death (PCD) through a BCL-2 sensitive pathway. In: FASEB Journal. 1998 ; Vol. 12, No. 5.
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