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. 2001 Jul;125(1):117-22.
doi: 10.1046/j.1365-2249.2001.01560.x.

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  1 , D Serrano, Z Zhou, I George, K Becker, C Cunningham-Rundles
Affiliations

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 et al. Clin Exp Immunol. 2001 Jul.

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.

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Figures

Fig. 1
Fig. 1
Percentage of Fas expression on T cells from 40 CVI patients and 32 normal subjects. n.s. not significant. Horizontal lines represent the median values.
Fig. 2
Fig. 2
FasL mRNA expression in lymphocytes from six normal subjects (Nl) and eight CVI patients (P1-P8). + + positive control (PBMC cultured in the presence of PHA and IL2 for 4 days); C = negative control; MW = molecular weight marker.
Fig. 3
Fig. 3
TNF-RI and β-actin mRNA expression in CD4+ T cells from six CVI patients and six normal controls. N = negative control, M = molecular weight marker.
Fig. 4
Fig. 4
TNF-RII and β-actin mRNA expression in CD4+ T cells from six CVI patients and six normal controls. N = negative control, M = molecular weight marker.
See this image and copyright information in PMC

References

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