Monitoring and modulation of immune reactivity in human transplant recipients

In this study parameters of humoral antibody (HA) and cell-mediated immunity (CMI) were measured before and after transplant in 44 renal transplant patients. The results indicated that, before transplant, CMI parameters but not HA measurements correlated with early graft rejection crises. In antithymocyte globulin (ATG)-treated patients, a striking loss of early rejection activity occurred which correlated with ablation of T cells in the peripheral blood. ATG-treated patients also had a marked loss of T cell reactivity, as measured by phytohemagglutinin (PHA) blastogenesis and these parameters also correlated with allograft reactivity. Concanavalin A (Con-A) reactivity, however, did not correlate well with early rejection activity. Triple drug therapy with ATG, but not prednisone-Imuran therapy, caused a marked fall of T cell levels and reactivity within hours of the first dose of ATG. None of the ATG-treated patients had irreversible or progressive rejection in the first month after transplant and only 32 percent of patients had rejections, of which more than 70 percent were Type I. A "permissive" level of T cells of about 20 percent of normal was associated with over 95 percent of acute rejection crises, whereas no correlation of a variety of humoral antibody parameters and rejection has been seen in our unit. These studies suggest a primary role of the T cell in early allograft reactivity and indicate that future immunosuppressive techniques for human transplantation should be directed toward effective monitoring and modulation of T cell levels and reactivity in the early post-transplant period.