[Previous Months][Date Index][Thread Index][Join - Register][Login]
[Message Prev][Message Next][Thread Prev][Thread Next]


Pancreas Islet Allotransplantation Maintained With 2 Weeks of 
WESTPORT, CT (Reuters Health) Jun 01 - 

Researchers have for the first time succeeded in transplanting and 
maintaining isolated pancreas islet cells into diabetic rhesus monkeys 
without long-term sustained immunosuppressive therapy, according to a report 
in the June issue of Diabetes. Dr. Francis T. Thomas, of the University of 
Alabama at Birmingham, and colleagues induced diabetes in 11 rhesus macaques 
with intravenous streptozotocin. Islet cell donors were selected to have 
multiple donor major histocompatibility complex mismatches with the diabetic 
recipients. For immunosuppression, "we used a new drug we developed which 
wipes out the CD3-epsilon receptor of T cells, including most importantly the 
T cells in the sessile compartments, such as the lymph nodes and spleen," Dr. 
Thomas told Reuters Health. The research team also used 15-deoxyspergualin 
(DSG) after discovering that it blocks maturation of dendritic cells that 
present foreign antigens to T cells, Dr. Thomas said. A 2-week tolerance 
induction protocol was initiated on the day of transplantation. Three 
protocols were used, anti-CD3 or DSG, or both. The macaques also received 
methylprednisolone on days 0 to 2. Within 3 days after the transplant, the 
recipients exhibited normal nonfasting blood glucose levels in the absence of 
exogenous insulin, the investigators report. All seven animals that received 
the combination tolerance induction protocol maintained prolonged graft 
survival, four for more than a year. The remaining four macaques failed to 
become long-term survivors. None of the recipients exhibited IgG- or 
IgM-positive flow cytometry antidonor crossmatches, although long-term 
survivors were immunocompetent with respect to a microbial antigen. Between 6 
months and a year after transplantation, peripheral and total T-cell counts 
recovered to their pretransplant levels. T-cell amplification was limited, as 
seen by a lower response to an antigen to which the donor were previously 
unexposed, Dr. Thomas' group notes. The investigators also observed 
"prominent and sustained expression" of interleukin-4 and -10, and normal 
levels of gamma-interferon. These latter findings indicate downregulation of 
peripheral T-helper-2 responses, the investigators write. This suggests, they 
add, that "an immunoregulatory rather than a deletional process underlies 
this operational tolerance model." Dr. Thomas noted that the islet 
transplantation procedure does not require hospitalization, and can be done 
in a radiology department using duplex Doppler to image the portal vein, into 
which the cells are injected. "The patient then gets off the table and goes 
home," he added. Dr. Thomas's group has also demonstrated the potential for 
using live donors, having achieved successful transplantation of two animals 
from one donor pancreas. He said that they have applied to the FDA to begin 
testing the new CD3 immunotoxin in a phase I clinical trial. 
Diabetes 2001;50:1227-1236. 
for HELP or to subscribe/unsubscribe, contact: HELP@insulin-pumpers.org
send a DONATION http://www.Insulin-Pumpers.org/donate.shtml