Peptide Immunotherapy

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In vitro and in vivo experimental models

The concept of therapeutic, antigen-specific targeting of T cells for the prevention and treatment of immunologic diseases developed from in vitro studies documenting the effects of high-dose peptide presentation between T cells. CD4+ helper T-cell clones were rendered refractory to antigen stimulation following pretreatment with supraoptimal concentrations of specific peptide [2]. Because antigen-presenting cells were absent, presentation of peptide to T-cell receptors most likely occurred

Autoimmunity

Peptide immunotherapy has been evaluated in small clinical studies with varying degrees of success. Most studies have focused on individuals with allergic disease, but some have also been performed in autoimmune disease including type I diabetes, rheumatoid arthritis, and multiple sclerosis. In many autoimmune diseases, it remains unclear which antigens should be selected as targets for intervention. Multiple sclerosis studies have focused on peptides from MBP, whereas two recent studies have

Mechanisms of peptide-induced tolerance

Immunologic tolerance in the T-cell compartment is likely to arise through systemic presentation of peptides (which are delivered to the immune system in saline without adjuvant and at very low doses) to naïve T cells by nonprofessional antigen-presenting cells and steady state (quiescent) dendritic cells, both of which are known to induce tolerogenic T-cell responses [41]. Because the peptides are encountered in a noninflammatory environment, the T-cell response will be one of tolerance

The role of peptide dose in therapy

Little is known about the most effective dose for induction of tolerance through peptide therapy. In mice, tolerogenic peptide doses range from a few micrograms [45] to milligrams [46]. By delivering T-cell epitopes directly to dendritic cells in vivo, it has recently been shown that doses as small as 500 pg can induce tolerance in a murine model [47]. Fundamental differences may exist in the mechanisms of low- and high-dose tolerance. High-dose protocols have been associated with clonal

Summary

Synthetic peptides representing T-cell epitopes of allergens and autoantigens have been employed to induce antigen-specific tolerance in vivo in experimental models and the clinical setting. Delivery of peptides orally or by injection leads to reduced reactivity to antigen accompanied by the induction of T cells with a regulatory phenotype. In most models, production of IL-10 (and occasionally TGF-β) has been increased, whereas PBMC secretion of Th1 and Th2 cytokines is reduced. Peptide therapy

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