Induction of tolerance to an allogeneic graft without the need for nonspecific immunosuppression is a major goal of transplantation therapy. We have shown that treatment with molecularly engineered, allochimeric [alpha(1h)(1/u)]-RT1.Aa class I MHC antigens bearing donor-type Wistar-Furth (WF, RT1.A(u)) or Lewis (LEW, RT1A(1)) amino acid substitutions for host-type ACI (RTI.A(a)) sequences in the alpha(1)-helical region induces donor-specific tolerance to cardiac allografts in rat recipients. The mechanisms involved in the establishment and maintenance of specific allograft tolerance are still not fully understood. It is now clear that acquisition of transplantation tolerance is an active, highly regulated, multistep process. According to the pool size model of allograft tolerance, the allograft outcome, rejection, or tolerance often depend on the balance between cytopathic and regulatory T cells (T-regs). This study examined mechanisms of chronic rejection (CR) development on a model of cardiac transplant tolerance after adoptive transfer of T-regs followed by allochimeric therapy. Generation of T-regs was demonstrated in vitro by MLR coculture and confirmed by adoptive transfer of T cells from primary recipients to secondary hosts. To confirm the true nature of regulatory cells, we performed a second transfer into tertiary recipients. Unlike T-regs from tolerant hosts, T cells from naive rats did not prolong graft survival. Histological evaluation of T-regs-transfected groups showed absence of visible CR. In contrast, T-regs generated in recipients after high-dose cyclosporine treatment failed to inhibit CR in transferred singeneic recipients. Allochimeric therapy triggers generation of unique regulatory lymphocytes that mitigate development of chronic rejection through regulation of anti-inflammatory mechanisms and down-regulation of alloantibody response.

Animals↗

PubMedDate not supplied

Nutritional outcomes following pediatric intestinal transplantation.

BACKGROUND: This study sought to describe the long-term nutritional outcomes of children after intestinal transplant (SBT). METHODS: Between 1991 and March 2005, 30 children received 33 SBT at a single center. Eligibility criteria included patient and graft survival >6 months. Weight, height, albumin, prealbumin, zinc (Zn), and essential fatty acid (EFA) levels were reviewed retrospectively. RESULTS: The 19 patients who met inclusion criteria had a median age at SBT of 2.9 years. The majority of patients were male, Latino, transplanted for necrotizing enterocolitis and received combined liver-SBT. All patients were weaned off total parenteral nutrition to elemental formula at a mean of 39 days post-SBT. Seventeen of 19 patients were Zn deficient and four patients were EFA deficient post-SBT. CONCLUSIONS: Pre-SBT most subjects were significantly deficient in anthropometric and biochemical parameters. Post-SBT the mean Z score for weight and height improved significantly at year 1, then leveled off in year 2. Serum protein levels improved from pre-SBT, yet remained low-normal. Zn deficiency was seen frequently after SBT and is under investigation. Children who developed EFA deficiency were on the same formula, receiving inadequate EFA supplementation. Successful SBT was associated with growth and maintenance of serum nutritional parameters but not with significant catch-up growth.

Adolescent↗

PubMedDate not supplied

Immunosuppressant neurotoxicity in liver transplant recipients. Clinical challenges for the consultation-liaison psychiatrist.

Neuropsychiatric problems are common among liver transplant recipients, and immunosuppressant neurotoxicity is an important etiologic factor in the posttransplant period. Four typical cases of immunosuppressant neurotoxicity are presented from the clinical experience of the University of California, Los Angeles-Dumont Liver Transplant program. All patients presented with acute behavioral symptoms and received urgent psychiatric consultation; each proved to be suffering from a variant of immunosuppressive-related neurotoxicity. Correlative neuroimaging studies and descriptions of clinical course are included. Psychiatrists are urged to become familiar with the signs, symptoms, differential diagnosis, neuroimaging findings, and management of immunosuppressive neurotoxicity and secondary psychiatric disorders in solid organ recipients.

Adult↗

PubMedDate not supplied