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PubMed1990

Strategies of immunosuppression in cardiac transplantation.

Immunosuppression for cardiac transplantation, as currently practiced, is based to a large extent on clinical trials that can best be characterized as single-institutional, uncontrolled, or historically controlled studies. While these non-randomized, retrospective studies clearly advanced the science and art of cardiac transplantation to the point that survival rates approaching 90% at 1 year are achievable, the specific immunosuppressive protocols used at any given institution are likely based more on the individual transplant surgeon's or physician's training and experience, than on a firm scientific basis. Thus, a significant lack of uniformity exists among transplant centers in virtually all phases of immunosuppression. More clinical and basic research efforts are needed to unify immunosuppressive strategies following cardiac transplantation. In the future, greater individualization of therapy is likely to occur and more prospectively randomized, multi-center trials are likely to be carried out, particularly in the area of early rejection prophylaxis.

Antibodies, Monoclonal↗
PubMed1990

Effective induction immunosuppression for cadaver renal transplantation at the St. Francis Regional Medical Center.

The OKT3 induction protocol, when compared to a conventional drug protocol, resulted in an improvement in both short- and long-term patient and graft survival, especially in patients receiving a primary transplant. The 1-year allograft survival in primary transplants receiving OKT3 induction was 91% and the T1/2 of 13.5 years. This was accomplished while still being able to minimize the total drug dose of Aza, Pred, and CsA, thereby minimizing clinical complications. The use of OKT3 did not increase infections or malignant complications. This resultant significant improvement supports the passenger leukocyte theory of stimulation for allograft rejection. Further graft survival improvement in histodisparate allografts might be accomplished by OKT3 induction in concert with other methodologies that can control this cell type. The HLA antigens may not be as large an obstacle to grafting as previously suggested.

Antibodies, Monoclonal↗
PubMed1990

Renal transplantation at the Washington Hospital Center: experience with OKT3 and Minnesota antilymphoblast globulin for induction of immunosuppression.

These data demonstrate excellent long-term patient and graft survival rates when cytolytic induction therapy is combined with sequential addition of CsA. OKT3 and MAG produce virtually indistinguishable outcomes with low rates of rejection and DGF. The frequency of serious posttransplant complications, infection, rejection, and malignancy was low. Although both MAG and OKT3 are effective, each has its drawbacks. Problems associated with MAG therapy are leukopenia, thrombocytopenia, cumbersome administration, and difficulty monitoring the patient's specific level of induced immunosuppression. OKT3 is simpler to administer, easy to monitor, but first dose reactions may produce additional graft injury. Furthermore, OKT3 may not protect completely against all mechanisms of cellular rejection. In our patient population, the best results occurred when kidneys functioned immediately, when CsA was introduced promptly, and when there were several days of overlap, with MAG or OKT3, especially when OKT3 was used as the induction agent.

Adult↗
PubMed1989

Temperature requirements and kinetics of T cell signaling. Velocity of triggering correlates with functional effects of anti-CD3 mAb.

Antibody reactive with the CD3 complex on the surface of T lymphocytes can either: inhibit CTL lysis of target cells expressing Ag; or redirect CTL to lyse target cells expressing FcR in the absence of Ag expression. To investigate these phenomena we examined the effect of anti-CD3 mAb on two indicators of CTL activation, the release of esterase and target cell lysis. Esterase release by long term allo-reactive human CTL in response to target cells (JY or HLA transfected K562 cells) was found to be Ag specific and correlate with target cell lysis. Addition of anti-CD3 to either JY targets or K562 cells expressing FcR resulted in a high level of esterase release. Triggering of esterase release was found with both soluble intact and Fab fragment of anti-CD3 in the absence of cells expressing measurable FcR. This apparent FcR-independent triggering of esterase release occurred at 37 degrees C but not at 24 degrees C. In contrast esterase activity was released from CTL at both 24 and 37 degrees C in response to intact target cells, JY or K562 cells plus intact anti-CD3 mAb. Addition of anti-CD3 mAb, at a level capable of blocking target cell lysis by greater than 50%, resulted in an initial velocity of esterase release almost twice that found in response to JY target cells. With a low level of anti-CD3 mAb, able to block JY lysis by approximately 10%, the initial rate of esterase release was much slower than that found in response to target cells. In contrast when FcR+ cells, K562, were added along with a low level of anti-CD3 the initial velocity of esterase release was about twofold more than the velocity of esterase release triggered by soluble anti-CD3 alone. These results indicate that soluble antibody can trigger long term active CTL and the velocity of this triggering correlates with anti-CD3-mediated inhibition as well as redirected lysis.

Antibodies, Monoclonal↗
PubMedDate not supplied

Long-term follow-up of heart transplant recipients treated with murine antihuman mature T cell monoclonal antibody (OKT3): the Loyola experience.

We describe the long-term follow-up of 25 patients treated with murine antihuman mature T cell (OKT3) monoclonal antibody at Loyola University Medical Center. After OKT3 rescue therapy, 12 patients were monitored for 16.5 +/- 6.5 months. Twenty-two moderate and three severe rejection episodes occurred 11 to 469 days (166.8 +/- 126.0) after OKT3 therapy in nine of 12 patients. During the follow-up period three patients died, and one required retransplantation because of recurrent rejection. The coronary arteries of three failed allografts had severe intimal thickening and infiltration with lymphocytes. Thirteen patients received OKT3 for prophylactic immunosuppression, and their course was compared to that of 13 patients who underwent transplantation during the same period but were given prophylactic horse antihuman thymocyte globulins (HATG). There were no differences between the two drugs with respect to long-term incidence and severity of rejection and infection, cardiac allograft function, and survival. Our results indicate that, despite successful reversal with OKT3, heart transplant recipients with refractory rejection remain plagued by recurrent rejection. Cardiac allografts in recipients who die as a result of recurrent rejection show evidence of immune-mediated vasculitis, which results in severe and diffuse coronary luminal narrowing. OKT3 and HATG appear to be equally effective for rejection prophylaxis.

Adult↗