Immobilized anti-CD5 together with prolonged activation of protein kinase C induce interleukin 2-dependent T cell growth: evidence for signal transduction through CD5.
Monoclonal antibodies (mAb) identifying the CD5 antigen were used to stimulate human peripheral blood T lymphocytes. Three out of three anti-CD5 mAb, 10.2, OKT1 and anti-Leu-1 induced vigorous proliferation of purified T cells in the presence of 1.6 nM phorbol 12-myristate 13-acetate (PMA). Immobilization of anti-CD5 mAb on a solid support was necessary for the induction of a proliferative response. Neither 1.6 nM PMA, nor immobilized anti-CD5 mAb were mitogenic as a sole stimulus. mAb identifying CD4, CD7, CD11a, CD18, and major histocompatibility complex class I molecules were not comitogenic with PMA. Anti-CD5/PMA-induced cell proliferation proceeded by an interleukin 2 (IL 2)-dependent mechanism, as was demonstrated by the cell surface expression of the p55 chain of the IL 2 receptor (IL 2R), the production of IL 2 and the inhibition of the proliferative response by anti-IL 2R mAb anti-Tac. There was no strict requirement for detectable numbers of monocytes, although cell proliferation could be enhanced by the monocyte-derived cytokines IL 1 and IL 6. Phorbol 12,13-dibutyrate and mezerein could substitute for PMA in this activation pathway, but synthetic diacylglycerols and phorbol esters that do not activate protein kinase C (PKC) could not, indicating a need for prolonged activation of PKC. T cells activated by anti-CD5/PMA are sensitive to inhibition by cyclosporin A (CsA) and by prostaglandin E2 (PGE2). This contrasts with anti-CD28/PMA-induced T cell proliferation, which is resistant to CsA and PGE2. Cell surface expression of CD5 was strongly up-regulated by PMA, whereas CD3 expression was down-regulated. We conclude that T cell activation can be triggered by engagement of CD5 by immobilized anti-CD5 mAb, combined with prolonged activation of PKC. These data support a role for CD5 as an independent signal transducing molecule.
Vandenberghe
P
P
Department of Internal Medicine and Pathophysiology, Faculty of Medicine, University of Leuven, Belgium.
Ceuppens
J L
JL
D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D018956:CD5 Antigens; D003524:Cyclosporins / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D011493:Protein Kinase C / Q000187:drug effects / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011990:Receptors, Transferrin / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D018956:CD5 Antigens; D003524:Cyclosporins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate