T cells from patients with Hodgkin's disease have a defective T-cell receptor zeta chain expression that is reversible by T-cell stimulation with CD3 and CD28.
To investigate the mechanisms underlying the deficiency of T lymphocytes from patients with Hodgkin's disease, we investigated the expression of the T-cell receptor (TCR) zeta chain in patients with Hodgkin's disease. By flow cytometry using an anti-zeta chain monoclonal antibody, peripheral blood T lymphocytes from patients with untreated Hodgkin's disease were shown to express decreased levels of the TCR zeta chain. After stimulation by combined CD3 and CD28 cross-linking, T cells from Hodgkin's disease patients upregulated zeta chain protein expression to normal values within 48 hours and achieved a cytolytic potential and levels of interleukin (IL)-2 secretion that were not different from T cells obtained from healthy controls. These results show that downregulation of the TCR zeta chain in Hodgkin's T lymphocytes is a reversible event. Costimulation of CD3 and CD28 is a novel approach for overcoming the T-cell deficiency in Hodgkin's disease and might be exploited clinically. As upregulation of the zeta chain can also be achieved using bispecific monoclonal antibodies (BI-MoAbs) with specificity for tumor antigens and CD3 and CD28, respectively, an immunotherapy with CD3/CD30 and CD28/CD30 Bi-MoAbs may overcome and should therefore, not be jeopardized by the inherent T-cell deficiency in patients with Hodgkin's disease.
Renner
C
C
Medical Department I, University of the Saarland, Homburg, Germany.
Ohnesorge
S
S
Held
G
G
Bauer
S
S
Jung
W
W
Pfitzenmeier
J P
JP
Pfreundschuh
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006689:Hodgkin Disease / Q000150:complications / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D002118:Calcium