Induction of hyperacute rejection of skin allografts by CD8+ lymphocytes.

Background: Second-set rejection is generally regarded as a phenomenon mainly mediated by humoral cytotoxic antibodies, although a few discordant data have been presented. In the reported experiments, we have taken advantage of the absence of production of specific cytotoxic alloantibodies contrasting with the normal development of transplantation cellular immunity, in two murine models: chimeric mice and RAG mice.

Methods: Chimeras (BALB/c-->CBA) were obtained by transplantation of 2x10(7) fetal liver cells from BALB/c (H-2d) mice to lethally irradiated CBA (H-2k) mice.

Transplantation of fetal liver cells corrects accumulation of lipids in tissues and prevents fatal neuropathy in cholesterol-storage disease BALB/c mice.

The cholesterol storage disease (CSD) BALB/c mouse represents a model of the Niemann-Pick type C (NPC) disease. It is characterized by the accumulation of unesterified cholesterol within various tissues, resulting in fatal neurological lesions. Transplantation of 6x10(6) fetal liver cells from normal allogeneic CBA mice into lethally irradiated CSD mice led to reconstitution of the recipient mice with donor cells.

Prolongation of skin allograft survival in mice following administration of ALLOTRAP.

Recently, Clayberger et al. demonstrated that ALLOTRAP, small synthetic peptides derived from a conserved region of the alpha 1 helix of certain HLA class I molecules, inhibited human CTL responses in vitro. In rats, ALLOTRAP 07 therapy combined with a subtherapeutic dose of cyclosporine led to the permanent acceptance of heart allografts.

Two novel vitamin D analogues, KH 1060 and CB 966, prolong skin allograft survival in mice.

KH 1060 and CB 966, two novel analogues of 1,25-dihydroxyvitamin D3(1,25(OH)2D3), were found to significantly delay the rejection of allogeneic skin grafts in CBA (H-2k) recipient mice, transplanted with skin from C57Bl/6 (H-2b) donor mice. Graft survival was assessed in mice treated with KH 1060 or CB 966 until the day of rejection, in comparison to mice treated with vehicle, 1,25(OH)2D3 or cyclosporin A (CsA). The mean graft survival time in days was found to be: 16.

The place of fetal liver transplantation in the treatment of inborn errors of metabolism.

Over the last 16 years, 202 fetal tissue transplants have been performed in our department to treat 29 patients with severe inborn errors of metabolism without immunodeficiency, 26 patients with congenital and severe immunodeficiency diseases, and 2 patients with severe aplastic anaemia. The actuarial survival curve of patients with inborn errors of metabolism treated with fetal liver transplantation shows a 12-year survival of 77%. The condition of many of these patients has been improved by the treatment, but transplantation has had to be repeated in order to maintain clinical amelioration.

[Lysosomal enzyme deficiency: in vitro correlation of deficient cells using a conditioned medium or by co-culturing with non-deficient cells].

We demonstrate that lysosomal enzyme (alpha-L-fucosidase) can enrich deficient fibroblasts, with purified enzyme brought by the medium, or with an enzyme supply by various cell sources. The co-culture systems lead to a deficient cell correction, whatever donor cells are lymphocytes or lymphoblastoid cells. This correction arise only with alive cells, and is strongly inhibited by mannose-6-phosphate.

Survey of experimental data on fetal liver transplantation.

Fetal liver transplantation has been shown to induce hematological and immunological reconstitution in irradiated rodents, dogs, horses, and sheep. Engraftment and reconstitution without GvHD has been readily obtained using histocompatible donors. When mismatched fetal donors were used, a comparatively larger number of donor cells was required, in addition to pre-treatment of host with higher doses of irradiation or irradiation plus chemotherapy.

Identification of denatured enzyme proteins in sodium dodecyl sulfate polyacrylamide gels.

A simple modification of the immunological sandwich method of Muilerman et al. for the identification of denatured enzyme proteins in sodium dodecyl sulfate-polyacrylamide gels is described, enabling the method to be used in principle for any enzyme whose activity is not inhibited by binding to antibodies. An immunological sandwich consisting of denatured enzyme, antibodies, and native enzyme is formed on a nitrocellulose filter blot of the gel, the filter is divided into strips, and each strip is tested for enzyme activity.