Characterization of the specificity and duration of T cell tolerance to intranasally administered peptides in mice: a role for intramolecular epitope suppression

Mucosal administration of antigens in experimental animals leads to the induction of peripheral T cell tolerance. We have previously reported that in H-2b mice, intranasal (i.n.) or oral administration of a peptide containing the immunodominant T cell epitope will down-regulate the function of CD4+ T cells reactive with Der P 1, a major target antigen in both B and T cell responses to house dust mite. In the present study we have investigated the tolerogenicity of peptides containing both dominant and subdominant determinants when given i.n. to nalve mice. Induction of tolerance by the nasally administered immunodominant peptide leads to a diminution in all T cell-derived cytokines and modulation of delayed-type hypersensitivity responses, but IgE production did not seem to be affected, furthermore the induction of T cell tolerance was stable, lasting beyond 6 months. We have also examined the specificity of intramolecular epitope suppression which is a feature of mucosal tolerance induced by nasally administered peptides and demonstrate that regulatory CD4+ T cells may exert their suppressive effect by linked recognition of epitopes on the same or neighbouring antigen-presenting cells.      

Peptide-induced deletion of CD8 T cells in vivo occurs via apoptosis in situ

The ultimate fate of T cells undergoing antigen-induced cell death in vivo remains controversial. Whereas apoptosis of CD4+ T cells driven by superantigen is readily detectable in lymphoid organs, CD8+ T cells have been reported to disappear from the lymphoid organs and accumulate in the liver where they undergo apoptosis. Using transgenic mice that produce large numbers of ovalbumin-specific CD8+ T cells (OT-I cells), we were able to investigate the events that follow soluble peptide administration in an independent CD8+ T cell system. Here we show that the OT-I cells undergo proliferation and apoptosis in situ in lymphoid organs in response to antigenic stimulation with no evidence for liver involvement. This is similar to the course of events found for CD4+ T cell activation and counters the view that the liver is a general site for CD8+ T cell clearance following antigen-specific activation.      

Failing arteriovenous dialysis fistulas: evaluation and treatment

A total of 31 patients with 45 episodes of failing arteriovenous dialysis fistulas was studied. Fistula failure was usually due to venous and/or anastomotic stenosis, often in conjunction with thrombosis. Abnormalities were treated by percutaneous dilation and occasionally streptokinase infusion. Most complications and failures occurred either in patients with recently created fistulas or in those with multiple or long segment stenosis associated with thrombosis. Patients with a single nonobstructing stenosis were very successfully treated with percutaneous techniques, which are the treatment of choice for this condition.