title: APL1, an altered peptide ligand derived from human heat-shock protein 60, increases the frequency of Tregs and its suppressive capacity against antigen responding effector CD4 + T cells from rheumatoid arthritis patients.
abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by a chronic relapsing-remitting joint inflammation. Perturbations in the balance between CD4 + T cells producing IL-17 and CD4 + CD25(high)FoxP3 + Tregs correlate with irreversible bone and cartilage destruction in RA. APL1 is an altered peptide ligand derived from a CD4+ T-cell epitope of human HSP60, an autoantigen expressed in the inflamed synovium, which increases the frequency of CD4 + CD25(high)FoxP3+ Tregs in peripheral blood mononuclear cells from RA patients. The aim of this study was to evaluate the suppressive capacity of Tregs induced by APL1 on proliferation of effector CD4+ T cells using co-culture experiments. Enhanced Treg-mediated suppression was observed in APL1-treated cultures compared with cells cultured only with media. Subsequent analyses using autologous cross-over experiments showed that the enhanced Treg suppression in APL1-treated cultures could reflect increased suppressive function of Tregs against APL1-responsive T cells. On the other hand, APL1-treatment had a significant effect reducing IL-17 levels produced by effector CD4+ T cells. Hence, this peptide has the ability to increase the frequency of Tregs and their suppressive properties whereas effector T cells produce less IL-17. Thus, we propose that APL1 therapy could help to ameliorate the pathogenic Th17/Treg balance in RA patients.
authors.affiliation: Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, 11300, Cuba.|Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Ariana
authors.initials: A
authors.lastname: Barberá
authors.affiliation: Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, 11300, Cuba.
authors.forename: Noraylis
authors.initials: N
authors.lastname: Lorenzo
authors.affiliation: Infectious Diseases and Immunology Department, Faculty of Veterinary Medicine, University of Utrecht, P.O. Box 80165, NL-3508 TD, Utrecht, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van Kooten
authors.affiliation: Department of Rheumatology and Clinical and Laboratory of Translational Immunology, University Medical Centrum Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Joel
authors.initials: J
authors.lastname: van Roon
authors.affiliation: Department of Pediatric Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.affiliation: Institute of Rheumatology, Ave 10 of October, No. 130, Havana, Cuba.
authors.forename: Dinorah
authors.initials: D
authors.lastname: Prada
authors.affiliation: Institute of Rheumatology, Ave 10 of October, No. 130, Havana, Cuba.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gómez
authors.affiliation: Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, 11300, Cuba.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Padrón
authors.affiliation: Infectious Diseases and Immunology Department, Faculty of Veterinary Medicine, University of Utrecht, P.O. Box 80165, NL-3508 TD, Utrecht, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.affiliation: Infectious Diseases and Immunology Department, Faculty of Veterinary Medicine, University of Utrecht, P.O. Box 80165, NL-3508 TD, Utrecht, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Broere
authors.affiliation: Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, 11300, Cuba. mcarmen.dominguez@cigb.edu.cu.
authors.forename: María
authors.initials: M
authors.lastname: Del Carmen Domínguez
mesh_terms: D000328:Adult; D000368:Aged; D000941:Antigens / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: C000614307:APL1 peptide, human; D000941:Antigens; D018834:Chaperonin 60; D008024:Ligands; D010455:Peptides
keywords: Altered peptide ligands; Heat shock protein 60; Regulatory T cells; Rheumatoid arthritis