Polyclonal rabbit gamma globulins against a human cytotoxic CD4 T cell clone. II. Use in prevention of rejection in kidney transplantation: a pilot study.
Antiblast globulins (GAB) were prepared by immunization of rabbits with activated T lymphocytes (AT) derived from a rejected kidney allograft. AT consisted of a CD4+ (CD3+, CD2+ TCR alpha+ beta+) clone cytotoxic for HLA DR8-positive targets. The immunizing cells were adapted to industrial growth conditions by repetitive stimulations with an EBV-transformed line from the kidney donor and recombinant IL-2. In the pilot study, GAB (1.0-1.5 mg/kg/day) was given in 12-hr infusions, in association with prednisone (Pred) 1 mg/kg/day and azathioprine (Aza) 2 mg/kg/day, as prophylactic treatment of rejection in 12 kidney-transplanted patients during the first 2 weeks postgrafting. GAB dosage was further adapted according to the level of circulating E-rosette-forming T cells (ERFT). Cyclosporine A (8 mg/kg/day) was given at day 14 as a monotherapy after Pred and Aza were progressively tapered. No patient died, but one kidney was lost from surgical complication. No rejection occurred under GAB treatment; 41% of patients had at least one episode in the first 3 months and 16% from 3 to 9 months. GAB side effects were minor (skin rash: 2, low grade fever: 4) except for one acute serum sickness. Platelet and white blood cell counts were unchanged, but there was a significant decrease in hemoglobin during the 2 weeks of GAB infusions. Few infectious episodes occurred (3 bacterial, 2 viral). GAB monitoring showed a dramatic drop in T11+, T3+, T4+, and T8+ circulating T cells (less than 10% of normal values between days 3 and 14), whereas EFRT cells had a delayed and somewhat lower decrease (less than 10% after day 6 only). Consequently, mean GAB doses had to be raised to 1.3 mg/kg/day at day 4 and 1.6 at days 8 and 14. This pilot study suggests that this new bioreagent should be of major interest in the prophylaxis and treatment of rejection in allograft recipients. A controlled study is in progress.
Hourmant
M
M
Service d'Immunologie Clinique et Transplantation C.H.U., INSERM U.211, Faculté de Médecine, Nantes, France.
Babinet
F
F
Cantarovich
D
D
Latour
M
M
Carcagne
J
J
Vie
H
H
Bonneville
M
M
Moreau
J F
JF
Carosella
E
E
Bignon
J D
JD
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D005434:Flow Cytometry; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D016030:Kidney Transplantation; D011817:Rabbits; D013601:T-Lymphocytes / Q000145:classification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D005719:gamma-Globulins / Q000009:adverse effects / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000961:Antilymphocyte Serum; D005719:gamma-Globulins