The effect of peripheral blood lymphocyte stimulation on zeta chain expression and IL-2 production in Hodgkin's disease

It has been reported that peripheral blood T cells and NK cells express red uced levels of the T-cell receptor signal-transducing zeta chain in Hodgkin 's disease (HD). The zeta chain has emerged as a key subunit of the T-cell antigen receptor, which plays a central role in the signal-transducing even ts leading to T and NK-cell activation. We were interested in determining w hether the low zeta chain expression in HD could be corrected by anti-CDS, anti-CD3-rIL-2 ex vivo stimulation. Zeta chain expression was analysed by d ual immunofluorescence on permeabilized cells before and after 72 hours of culture, The IL-2 concentration in the culture supernatants was measured by ELISA. Zeta chain was significantly reduced on unstimulated CD4(+), CD8(+) and CD56(+) cells from patients in active disease compared with normal sub jects. In patients in complete remission. the values were normal except for CD8(+) cells, on which zeta expression remained significantly reduced. Sti mulation with anti-CDS did not change zeta expression. Co-stimulation with rIL-2 increased but did not normalize the proportions of CD4(+)/zeta(+), CD 8(+)/zeta(+) and CD56(+)/zeta(+) cells and IL-2 production in active diseas e. Stimulation of cells from patients in clinical remission with anti-CD3()rIL-2 increased the proportion of CD8(+)zeta(+) cells and normalized IL-2 production levels. Considering the pivotal role of CD3-zeta in immune respo nse, our data suggest that successful immunotherapy approaches in active HD should consider inclusion of other potent cytokines, as well as geneticall y engineered tumour vaccines. (C) 2001 Cancer Research Campaign.