CD4+ TCR alpha beta+ T-cell clones derived shortly after allogeneic bone marrow transplantation: theophyllamine and verapamil inhibit proliferation of functionally heterogeneous T-cells.
CD4+ TCR alpha beta+ T-cell clones were prepared from three CML-patients 4-6 weeks after allogeneic bone marrow transplantation and the effects of theophyllamine and verapamil on clonal growth then assessed. Both drugs inhibited PHA-stimulated autocrine proliferation of clones as well as proliferation of clones dependent on exogenous growth factors. Inhibition was seen when using different accessory cells (PBM or BCL) during T-cell activation, and both for IL2- and IL4-dependent proliferation of previously activated T-cells. The isomer R-verapamil inhibited PHA-stimulated proliferation as well as IL2- and IL4-dependent T-cell proliferation. The drugs also inhibited proliferation of CD8+ T-cells. Although the T-cell clones were functionally heterogeneous and were derived from different patients and priming cultures, both drugs inhibited all clones investigated. However, the degree of inhibition varied between different clones.
Bruserud
O
O
Second Department of Internal Medicine, Tübingen University Medical Clinic, F.R.G.
Hamann
W
W
Patel
S
S
Pawelec
G
G
D000628:Aminophylline / Q000494:pharmacology*; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000032:analysis*; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014700:Verapamil / Q000494:pharmacology*
D015704:CD4 Antigens; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D000628:Aminophylline; D014700:Verapamil