Rejection prophylaxis with interleukin-2 receptor antibody BT 563: mechanisms of action on human cells.
We investigated the in vitro immunosuppressive effect of BT 563, a monoclonal antibody, against the alpha-chain of the human interleukin-2 (IL-2) receptor (p 55), which has been used to prevent transplant rejection in several clinical trials. We also measured the proliferative T cell alloresponse and pCTL frequencies of BT563-treated kidney transplant patients. In mixed lymphocyte cultures BT 563 caused a reduction of T cell proliferation to about 50%. This could not be reversed by the addition of exogenous IL-2. A more effective reduction (80%) was seen in the generation of cytotoxic T cells from CML cultures and at the clonal level. The specific T cell response after preincubation with antigen and BT 563 was not reduced so that BT 563 did not induce tolerance. The in vitro findings indicated that BT 563 had a significant but incomplete immunosuppressive effect. This correlated with the clinical course and ex vivo analysis of PBL from BT 563-treated patients after kidney transplantation.
Herwartz
C
C
Institute for Immunology, Kiel University, Kiel, Germany.
Steinmann
J
J
Bethke
U
U
Engemann
R
R
Gassel
J
J
Hoffmann
S
S
Leimenstoll
G
G
Timmermann
W
W
Müller-Ruchholtz
W
W
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C079843:inolimomab