EFFECTS OF PEPTIDE THERAPY ON EX-VIVO T-CELL RESPONSES

Citation
Gv. Marcotte et al., EFFECTS OF PEPTIDE THERAPY ON EX-VIVO T-CELL RESPONSES, Journal of allergy and clinical immunology, 101(4), 1998, pp. 506-513
Citations number
33
Categorie Soggetti
Immunology,Allergy
ISSN journal
00916749
Volume
101
Issue
4
Year of publication
1998
Part
1
Pages
506 - 513
Database
ISI
SICI code
0091-6749(1998)101:4<506:EOPTOE>2.0.ZU;2-N
Abstract
Background: Peptide therapy targets T cells directly with short peptid es containing multiple T-cell receptor epitopes. Murine studies sugges t T cell anergy as the mechanism of action; however, changes in T-cell cytokine profiles may be more relevant in human beings. Objective: We sought to study the effects of peptide therapy on ex rivet antigen sp ecific T-cell responses. Methods: Antigen-specific T cell lines were g enerated from subjects enrolled in a double-blind, placebo controlled, two-dose study of the ALLERVAX CAT therapeutic, containing Fel d 1 pe ptide (ImmuLogic Pharmaceutical Corp., Waltham, Mass.) (n = 7, 8, and 7, respectively, for groups receiving placebo, 75 mu g, or 750 mu g). Each subject had three lines propagated before and after receiving pep tide therapy; antigens used were cat hair extract, Fel d I peptides, a nd tetanus toroid (negative control), Proliferative responses and cyto kine generation from each line were assessed after two restimulations with antigen and autologous antigen-presenting cells. Results: The Fel d 1 peptide lines showed a dose-dependent decrease of IL-4 production (p = 0.02 and 0.025, respectively, for the 750 mu g group vs both the 75 mu g and placebo groups), IL-4 production from the cat hair allerg en extract lines and interferon-gamma production from both the Fel d 1 peptide lines and cat hair allergen extract lines showed no statistic ally significant changes. The control tetanus toroid lines showed no c hanges in cytokine production; there were no significant changes in pr oliferation with any of the antigens in any of the treatment groups. I n the clinical arm of the trial, only the 750 mu g dose of peptides pr oduced a significant response. Conclusions: Peptide therapy indices a significant, dose-dependent decrease in peptide-stimulated IL-4 produc tion, consistent with either a shift in T-cell phenotype or peptide-sp ecific T-cell tolerance.