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ANTI-CD8 ABROGATES EFFECT OF ANTI-CD4-MEDIATED ISLET ALLOGRAFT SURVIVAL IN RAT MODEL

ANTI-CD8 ABROGATES EFFECT OF ANTI-CD4-MEDIATED ISLET ALLOGRAFT SURVIVAL IN RAT MODEL DIABETES SEYDEL, K., Shizuru, J., Grossman, D., Wu, A., Alters, S., Fathman, C. G. 1991; 40 (11): 1430-1434

Abstract

We studied the effects of anti-CD4 treatment of diabetic ACI rats on the induction of tolerance to allogeneic (Lewis) islet allografts. When given as a 4-day treatment regimen, OX38, a mouse anti-rat CD4 antibody, caused depletion of greater than 80% of CD4+ cells from the peripheral blood of treated rats. After induction of diabetes (a single high-dose bolus of streptozocin) and 3 days after the initiation of anti-CD4 immunotherapy, recipient ACI rats were transplanted with fully allogeneic (Lewis) islets of Langerhans via the portal circulation. These transplanted islets were capable of returning the anti-CD4-treated ACI recipients to normoglycemia, which was maintained indefinitely in the absence of further immunosuppression. In contrast, treatment of recipient rats with OX8, an anti-CD8 monoclonal antibody (MoAb), induced only a slight prolongation of graft survival (less than or equal to 30 days). Further characterization of the cellular requirements for the induction of long-term transplantation survival revealed that successful pretransplantation anti-CD4 therapy could be ablated by the coincident treatment of recipient rats with depleting levels of anti-CD8 MoAb. These data point to the necessity of a regulator CD8+ cell in the induction of anti-CD4-mediated transplantation survival in this rat model of islet transplantation.

View details for Web of Science ID A1991GN93200010

View details for PubMedID 1834499