Lymphocyte stimulation by CD3-CD28 enables detection of low T cell interferon-γ and interleukin-4 production in rheumatoid arthritis

Catharina M. Verhoef*, J. A G Van Roon, M. E. Vianen, C. A F M Glaudemans, F. P J G Lafeber, J. W J Bijlsma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)


The analysis of cytokine production is increasingly important in defining the course of an immune response and in evaluating specific therapies of immune diseases. In rheumatoid arthritis (RA), a dysregulation in T1/T2 cell balance, as defined by the production of their specific cytokines, IFN-γ and IL-4, respectively, is suggested. A predominance of T1- cell mediated macrophage activity in the joint plays a key role in the destruction of articular cartilage and subchondral bone, whereas local T2 cell activity, mitigating disease, fails. However, analysis of the cytokines defining both T cell subsets is difficult and spontaneous production is often below detection limits. Several stimuli are therefore used to increase cytokine production. In the present study we examined whether stimulation of peripheral blood T cells in the context of mononuclear cells (PB MNC) by CD3- CD28 is a reliable method for assessing IFN-γ and IL-4 production and is representative for the spontaneous production of these cytokines. The production of IFN-γ and IL-4 following CD3-CD28 stimulation of RA PB MNC correlated significantly in a ratio 1: 1 with production following ionomycin- PMA stimulation. In samples with detectable spontaneous production of IFNγ and IL-4, production following CD3-CD28 stimulation was significantly higher than in stimulated samples with undetectable spontaneous production. Moreover, in the case of spontaneous production there was a significant positive linear correlation between the CD3-CD28 stimulated and spontaneous IFN-γ and IL-4 production, although production of both cytokines was not equally enhanced. Serial sampling did not show significant daily or weekly variation in stimulated cytokine production. The results demonstrate that a pecific T-cell stimulation by CD3-CD28 is a reliable way to enhance IFN-γ and IL-4 production above the detection limit and so measure the T1/T2 cell balance in RA.

Original languageEnglish
Pages (from-to)427-432
Number of pages6
JournalScandinavian Journal of Immunology
Issue number4
Publication statusPublished - 16 Oct 1999


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