PATTERNS OF ALLOSENSITIZATION IN ALLOGRAFT RECIPIENTS - LONG-TERM CARDIAC ALLOGRAFT ACCEPTANCE IS ASSOCIATED WITH ACTIVE ALLOANTIBODY PRODUCTION IN CONJUNCTION WITH ACTIVE INHIBITION OF ALLOREACTIVE DELAYED-TYPE HYPERSENSITIVITY

Background. The immunologic characteristics of experimental allograft acceptance remain ill-defined. This study evaluates humoral and cell-m ediated immunity in transiently immunosuppressed mice that have accept ed cardiac allografts, Methods. DBA/2-->C57BL/6 heterotopic cardiac al lograft recipients were immunosuppressed with either GK1.5 monoclonal antibody or gallium nitrate and monitored for donor-reactive delayed-t ype hypersensitivity (DTH) assessed by ear challenge and for alloantib ody production detected by flow cytometry. Results. Cardiac allograft function continued for >90 days in approximately 50% of GK1.5-treated and 97% of gallium nitrate-treated transplant recipients. All nonsuppr essed recipients lost graft function within 7 to 10 days. Among mice t hat accepted allografts, donor-reactive IgG was produced by about 50% of GK1.5 monoclonal antibody-treated mice and 80% of gallium nitrate-t reated mice. None of the these mice exhibited donor-reactive DTH respo nses, and all could down-regulate third-party DTH responses in a donor alloantigen-dependent manner. This down-regulation is not found in no nsuppressed allograft recipients or in naive mice. Importantly, transf er into SCID mice of splenocytes from mice that accepted allografts, b ut not naive splenocytes, provided them with a similar ability to acce pt cardiac allografts, even if the grafts co-expressed third-party all oantigens. Conclusions. IgG alloantibody production by murine cardiac allograft recipients is not a precise indicator of allosensitization l eading to either cardiac allograft rejection or acceptance. However, e xpression of alloreactive DTH is a reliable indicator of allosensitiza tion leading to acute rejection, and the absence of DTH in association with active DTH down-regulatory mechanisms is a reliable indicator of allograft acceptance in this experimental model. Thus, DTH analysis m ay hold more promise than alloantibody detection for clinical assessme nt of posttransplant immune status.