Immunosuppressive therapy abrogates unresponsiveness to renal allograft induced by thymic recognition of donor antigens.

This laboratory and others have previously shown that the intrathymic injection of donor cells or major histocompatibility complex allopeptides induced indefinite survival of a subsequent graft without immunosuppression. This approach may open interesting new perspectives for transplant medicine. Studies to explore the feasibility of the technique in humans can only be designed with some form of concomitant immunosuppression to avoid the risk of irreversible rejection in the case that the thymus approach fails.

Toward novel antirejection strategies: in vivo immunosuppressive properties of CTLA4Ig.

Allograft rejection is a process that depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules binds to their ligands, such as CD28 to the B7 molecules. We investigated the possibility that B7 blockade in vivo by the soluble CD28 receptor homolog CTLA4Ig modulates rejection process in a rat model of kidney allograft. Lewis rats orthotopically transplanted with MHC incompatible kidney from Brown-Norway rats were given an intraperitoneal injection of CTLA4Ig (0.

Blocking cell microtubule assembly inhibits the alloimmune response in vitro and prolongs renal allograft survival by inhibition of Th1 and sparing of Th2 cell function in vivo.

Colchicine inhibits cell microtubule assembly by binding to and preventing the polymerization of tubulin monomers. Although there are data to indicate that colchicine inhibits a variety of cell-mediated immune responses, the effects and mechanisms of inhibiting cell microtubule assembly on the alloimmune response have not been thoroughly investigated. It has recently been shown that colchicine prevents acute rejection and promotes the long-term survival of rat renal allografts.

Effects of angiotensin-converting enzyme inhibition on glomerular capillary wall ultrastructure in MWF/Ztm rats.

Previous studies have documented that treatment with angiotensin-converting enzyme (ACE) inhibitors prevents spontaneous proteinuria and enhances the glomerular ultrafiltration coefficient in male MWF/Ztm rats. The aim of this study was to study whether these beneficial effects of ACE inhibitors on glomerular capillary wall function are derived from the preservation of its ultrastructure. Conventional morphometrical analysis of kidney tissue, by light and electron microscopy, was used to quantify glomerular structural changes in the male MWF/Ztm rats treated with the ACE inhibitor cilazapril for 2 and 6 months and in age-matched untreated controls.

Dissociation between antiproteinuric and antihypertensive effect of angiotensin converting enzyme inhibitors in rats.

To clarify whether angiotensin converting enzyme (ACE) inhibitors prevent progressive renal injury directly by their antihypertensive effect we administered the ACE inhibitor lisinopril to male MWF/Ztm rats as a single daily dose that lowered blood pressure for only 9 of 24 h. We investigated the effects of this treatment in short- and long-term studies and compared them with another antihypertensive drug, the calcium channel blocker nitrendipine, given to partially control blood pressure as done with the ACE inhibitor. In untreated animals systemic hypertension, proteinuria, and glomerulosclerosis developed spontaneously with age, and lisinopril reduced systemic hypertension and prevented proteinuria and glomerular lesions.