POLYCLONAL RABBIT GAMMA GLOBULINS AGAINST A HUMAN CYTOTOXIC CD4 T CELL CLONEII. USE IN PREVENTION OF REJECTION IN KIDNEY TRANSPLANTATIONA PILOT STUDY
作者:
M. HOURMANT,
F. BABINET,
D. CANTAROVICH,
M. LATOUR,
J. CARCAGNE,
H. VIE,
M. BONNEVILLE,
J. MOREAU,
E. CAROSELLA,
J. BIGNON,
J. SOULILLOU,
期刊:
Transplantation
(OVID Available online 1989)
卷期:
Volume 48,
issue 2
页码: 260-263
ISSN:0041-1337
年代: 1989
出版商: OVID
数据来源: OVID
摘要:
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 (<10% of normal values between days 3 and 14), whereas EFRT cells had a delayed and somewhat lower decrease (<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.
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