PubMed Health⌕ Search

Biomedical subjects

M J Dallman

Publications and source records attributed to M J Dallman.

94 records · Page 6Linked to original sources

Human neural graft function in rats treated with anti-interleukin II receptor antibody.

Prolonged immunosuppression with cyclosporin A allows survival of human xenografts in the rat Parkinsonian model but the drug has side effects. Ideally immunosuppression should be of short duration, to minimize the chance of infection, yet be capable of supporting long term survival of the transplanted tissue. We report that short term treatment with an anti-rat interleukin II receptor (IL2R) monoclonal antibody (MAb) resulted in apparently permanent survival of human fetal dopaminergic grafts in "Parkinsonian" rats. The recipients remained healthy and the excellent survival of the transplants suggests that the antibody injection strategy would almost certainly abrogate allograft rejection and raises the possibility that xenogenic dopaminergic neurones could be used as donor tissue in humans.

Animals↗

Linked suppression in peripheral T cell tolerance to the house dust mite derived allergen Der p 1.

BACKGROUND: Peripheral tolerance is required to maintain balance within the immune system. A feature of peripheral tolerance is linked suppression, in which tolerance induced to a single T cell epitope inhibits the response to all epitopes in the same protein. It is suggested that this phenomenon is mediated by regulatory T cells through either the activity of immunopressive cytokines or direct cell contact. In previous experiments we failed to detect inhibitory cytokines when T cells from mice rendered tolerant by intranasal delivery of the immunodominant peptide of Der p 1 (p 1, 110-131) were restimulated with peptide in vitro. Therefore, the aim of this study was to determine if cognate interactions between T cells mediated by Notch/Delta signaling induce and maintain peripheral T cell tolerance. METHODS: Using in situ hybridization and viral mediated gene transfer, the expression and function of Delta1 were investigated in a murine model of T cell tolerance to Der p 1 in vivo. RESULTS: Delta1 expression is increased on peripheral T cells during the induction of tolerance with high-dose peptide delivered intranasally and when tolerant animals are rechallenged under immunogenic conditions. Peptide p 1, 110-131-specific CD4+ T cells transfected with Delta1 inhibited the response of antigen-primed T cells and induced linked suppression. CONCLUSIONS: High-dose peptide delivered intranasally induces transient expression of Delta 1 on inhibitory CD4+ T cells. Ligation of the Notch1 receptor on neighbouring T cells by Delta1+ regulatory T cells inhibits clonal expansion of the former and mediates linked suppression.

Allergens↗