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 reduced 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 events leading to T and NK-cell activation. We were interested in determining whether the low zeta chain expression in HD could be corrected by anti-CD3, anti-CD3-rIL-2 ex vivo stimulation. Zeta chain expression was analysed by dual 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 subjects. In patients in complete remission, the values were normal except for CD8+ cells, on which zeta expression remained significantly reduced. Stimulation with anti-CD3 did not change zeta expression. Co-stimulation with rIL-2 increased but did not normalize the proportions of CD4(+)/zeta(+), CD8(+)/zeta(+)and CD56(+)/zeta(+)cells and IL-2 production in active disease. 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 response, our data suggest that successful immunotherapy approaches in active HD should consider inclusion of other potent cytokines, as well as genetically engineered tumour vaccines.
Frydecka
I
I
Department of Haematology, Medical University, Pasteura 4, Wroclaw, 50-367, Poland.
Boćko
D
D
Kosmaczewska
A
A
Ciszak
L
L
Morilla
R
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019002:CD56 Antigen / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; C054979:antigen T cell receptor, zeta chain