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.