Enhanced T cell apoptosis in common variable immunodeficiency: Negative role of the fas/fasligand system and of the Bcl-2 family proteins and possible role of TNF-RS

M. Di Renzo, D. Serrano, Z. Zhou, I. George, K. Becker, C. Cunningham-Rundles

Research output: Contribution to journalArticlepeer-review

Abstract

CVI is a primary immunodeficiency characterized by a failure of B cell differentiation associated with an array of T cell defects, such as enhanced T cell apoptosis. In this study we investigated the mechanisms underlying CVI enhanced T cell death. We analysed both the expression of Fas using flow cytometry techniques and the expression of FasL mRNA using RT-PCR in CVI T cells. We could not find any significant differences between CVI and normal subjects with regard to Fas expression, although there was a subgroup of CVI patients with very high Fas expression which was accompanied by an up-regulation of FasL mRNA. However, attempts to induce Fas-mediated apoptosis in these high Fas expressing cells, as evaluated by propidium iodide staining and APO2.7 staining, were unsuccessful. We also investigated intracellular levels of Bcl-2, bcl-xl and bax in CD4 + and CD8 + CVI T cells, as well as the bax/Bcl-2 ratio, using flow cytometry techniques but could not detect any differences between CVI and normal subjects. Finally we analysed TNF-RI and TNF-RII mRNA expression in CD4 + and CD8 + CVI T cells using semiquantitative RT-PCR and found a significant increase in expression of both TNF-Rs in CD4 + T cells from CVI patients. Our data suggest that the increased expression of both TNF-Rs on T cells may be one of the mechanisms responsible for the accelerated T cell apoptosis in CVI.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalClinical and Experimental Immunology
Volume125
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Bcl-2 protein family
  • CVI
  • Fas/FasL
  • T lymphocytes
  • TNF-Rs

ASJC Scopus subject areas

  • Immunology

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