IngentaConnect Signalling molecules and cytokine production in T cells of multip...

Authors: Mozaffari F.¹; Hansson L.; Kiaii S.; Ju X.¹; Rossmann E.D.¹; Rabbani H.¹; Mellstedt H.; Österborg A.

Source: British Journal of Haematology, Volume 124, Number 3, February 2004 , pp. 315-324(10)

Abstract:

Summary

T-cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components of the T-cell receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four-colour flow cytometry was applied to study the surface bound molecules TCR, CD28, CD152 and CD154 involved in T-cell signalling and the signal transduction molecules CD3, p56^lck, p59^fyn, ZAP-70 and phosphatidyl-inositol-3 kinase (PI3-k) as well as the intracellular cytokines interferon- (IFN-), interleukin (IL)-4 and IL-2 as a functional read-out of non-stimulated and superantigen (staphylococcus enterotoxin B)-stimulated blood T cells of multiple myeloma (MM) patients at different stages of the disease. Multiple abnormalities were demonstrated in the CD4 and CD8 populations, both under non-stimulated and superantigen-stimulated conditions. There was a marked reduction, particular in advanced stage MM, in the proportion of CD4 and CD8 cells expressing CD28, CD152, CD3, p56^lck, ZAP-70 and PI3-k. The level of intracellular T-cell cytokines (IFN-, IL-2 and IL-4) was normal or increased in non-stimulated cells but activation-induced cytokine production was impaired. These results illustrated profound and multiple T-cell signalling defects, from the surface and down-stream, consistent with involvement of a master T-cell function, especially in advanced stage MM. These data should be taken into consideration when developing immune-based therapeutic approaches and when applying new emerging technologies that aim to restore T-cell functions.

Keywords: multiple myeloma; T cells; signal transduction molecules; activation markers; cytokines

Document Type: Research article

DOI: 10.1046/j.1365-2141.2003.04789.x

Affiliations: 1: Immune and Gene Therapy Laboratory, Cancer Centre Karolinska

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Signalling molecules and cytokine production in T cells of multiple myeloma-increased abnormalities with advancing stage