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. 1997 Nov;56(11):656–660. doi: 10.1136/ard.56.11.656

Decrease in peripheral type 1 over type 2 T cell cytokine production in patients with rheumatoid arthritis correlates with an increase in severity of disease

J A G van Roon 1, C Verhoef 1, J L A M van Roy 1, F Gmelig-Meyling 1, O Huber-Bruning 1, F Lafeber 1, J Bijlsma 1
PMCID: PMC1752286  PMID: 9462167

Abstract

Objectives—To compare peripheral type 1 (T1) and type 2 (T2) T cell activities in rheumatoid arthritis (RA) patients with that found for osteoarthritic (OA) patients and healthy controls and to correlate peripheral T1/T2 cell activity in RA with parameters of the disease.
METHODS—Peripheral blood mononuclear cells were isolated from patients with RA (n=66), OA (n=19), and healthy controls (n=15). Primary T cell activity in these mononuclear cells was enhanced by means of anti-CD3/anti-CD28, which mimicks stimulation of T cells by activation of the T cell receptor and a major co-stimulatory signal. Interferon gamma (IFNγ) production and interleukin 4 (IL4) production in the three groups were quantified as measures of T1 and T2 cell activity, respectively, and compared. Serum tumour necrosis factor α (TNFα), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and joint destruction assessed radiographically of RA patients were determined as parameters of disease activity and correlated with T1/T2 cell activity.
RESULTS—Peripheral T cells from RA patients produced significantly less IFNγ and more IL4 than T cells from both age and sex matched OA patients and healthy controls. Moreover, in RA patients both a decrease in IFNγ and an increase in IL4 production correlated with an increase in serum TNFα, ESR, CRP, and joint destruction. 
Conclusions—These results suggest a role for differential T cell activity in RA. In view of the intra-articular T1 cell predominance the results might be explained by selective T1 cell migration into the joint or peripheral suppression of T1 cell activity.



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Figure 1  .

Figure 1  

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IFNγ and IL4 production by anti-CD3/CD28 stimulated peripheral blood T cells (mononuclear cells) from patients with RA (n=66) and OA (n=19) and healthy controls (C, n=15). Data for a group of patients with RA matched for age and sex with OA patients and healthy controls are also shown (RAm). Means (SEM) are given. * Indicates a statistically significant difference between OA, controls, and RA patients (p⩽0.05).

Figure 2  .

Figure 2  

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Correlation of IFNγ and IL4 production by anti-CD3/CD28 stimulated peripheral blood T cells (mononuclear cells) from RA patients with serum TNFα.

Figure 3  .

Figure 3  

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Production of IFNγ and IL4 by anti-CD3/CD28 stimulated peripheral blood T cells (mononuclear cells) from RA patients divided according to the Steinbrocker radiological damage scores on hand radiographs. The numbers of patients per group were: I=14, II=19, III=25, and IV=8. * Indicates a statistically significant difference between group III or IV and group I (p⩽0.05).

Selected References

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