Renal allograft recipients generally need to take several immunosuppressive agents for life. Calcineurin inhibitors and glucocorticosteroids are the mainstays of most regimens but have undesirable chronic effects. We postulated that aggressive T-cell depletion combined with the newer immunosuppressant sirolimus would permit transplantation without multidrug treatment. We therefore tested T-cell depletion with rabbit antithymocyte globulin followed by sirolimus monotherapy in 12 patients in an open-label study. This approach was tolerated well, and all patients achieved excellent renal function, and most did not need chronic steroid treatment or calcineurin inhibitors. Rejection was typically correlated with low concentrations of sirolimus, indicating continued dependence on maintenance immunosuppression.

Twenty-one adult volunteers were immunized at monthly intervals with three doses of purified type 1 M protein of group A Streptococcus. The soluble vaccine in buffer was administered by aerosol spray into the nares and oropharynx; 23 control subjects received a buffer placebo in the same manner. Antibody responses were observed in sera and nasal washings of some but not all vaccines. Approximately 30 days after the last dose, all subjects were challenged with homologus streptococci applied by swab to the phayngeal-tonsillar areas. In a double-blind system of evaluation, physical signs and symptoms were followed for assessment of infection. Illness was defined on the basis of a positive throat culture, fever, a twofold increase in white blood cell count over baseline, exudative pharyngitis, and cervical adenopathy. By these criteria four vaccinees and 11 controls were obviously ill. One vaccinee and six controls were questionably ill, fulfilling some but not all of the criteria. sixteen vaccinees and six controls were not ill (P less than 0.001). Positive throat cultures were observed in five vaccines and 19 controls (P less than 0.001). Penicillin was administered five days after challenge. No poststreptoccal sequelae or other complication were observed. Thus local immunization with M protein apparently can prevent both colonization and clinical illness after challenge with homologous streptococci.

Aim/hypothesis-We measured serum C-peptide in many individuals with chronic type 1 diabetes (T1D) and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of such subjects' persistent anti-beta cell autoimmunity, we speculated that immunosuppression (to weaken the autoimmune attack) and euglycemia accompanying transplant-based treatments for type 1 diabetes (T1D) might promote recovery of T1D subject's native pancreatic beta cell function.Methods-We performed arginine stimulation tests in 3 islet transplant and 4 whole pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. We differentiated insulin secreted from the individual's native pancreatic beta cells and from allografted beta cells based upon each sampling site's C-peptide concentration and kinetics.Results-Selective venous sampling demonstrated that despite long-standing T1D, all 7 beta cell allograft recipients displayed evidence that their native pancreas was a source for secreted C-peptide. Even so, if chronic immunosuppression coupled with near normal glycemia improved native pancreatic C-peptide production, the magnitude of the effect was quite small.Conclusions/interpretation-While some native pancreatic beta cell function persists even years after disease onset in most with T1D, if prolonged euglycemia plus anti-rejection immunosuppressive therapy promotes improved the subjects' native pancreatic insulin production, the effect is small. We may have underestimated pancreatic regenerative capacity by studying only a limited subject number, or by creating conditions (e.g. high circulating insulin concentrations, or immunosuppressive agents toxic to beta cells) that impair beta cell function.

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