An epitope-specific DerG-PG70 LEAPS vaccine modulates T cell responses and suppresses arthritis progression in two related murine models of rheumatoid arthritis
| Autor: | Steve Cress, Roy E. Carambula, Júlia Kurkó, Ken S. Rosenthal, Harold L. Steiner, Daniel H. Zimmerman, Katalin Mikecz, Adrienn Markovics, Tibor T. Glant |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment T cell T-Lymphocytes Antigen presentation Arthritis medicine.disease_cause Epitope Article Autoimmunity Arthritis Rheumatoid 03 medical and health sciences Epitopes 0302 clinical medicine Immune system Medicine Animals Elméleti orvostudományok Aggrecans Mice Inbred BALB C Vaccines General Veterinary General Immunology and Microbiology business.industry Public Health Environmental and Occupational Health Immunotherapy Orvostudományok medicine.disease Disease Models Animal 030104 developmental biology Infectious Diseases medicine.anatomical_structure Treatment Outcome Immunology Peptide vaccine Molecular Medicine Female business 030215 immunology |
| Zdroj: | Vaccine. 35(32) |
| ISSN: | 1873-2518 |
| Popis: | Rheumatoid arthritis (RA) is an autoimmune joint disease maintained by aberrant immune responses involving CD4+ T helper (Th)1 and Th17 cells. In this study, we tested the therapeutic efficacy of Ligand Epitope Antigen Presentation System (LEAPS™) vaccines in two Th1 cell-driven mouse models of RA, cartilage proteoglycan (PG)-induced arthritis (PGIA) and PG G1-domain-induced arthritis (GIA). The immunodominant PG peptide PG70 was attached to a DerG or J immune cell binding peptide, and the DerG-PG70 and J-PG70 LEAPS vaccines were administered to the mice after the onset of PGIA or GIA symptoms. As indicated by significant decreases in visual and histopathological scores of arthritis, the DerG-PG70 vaccine inhibited disease progression in both PGIA and GIA, while the J-PG70 vaccine was ineffective. Splenic CD4+ cells from DerG-PG70-treated mice were diminished in Th1 and Th17 populations but enriched in Th2 and regulatory T (Treg) cells. In vitro spleen cell-secreted and serum cytokines from DerG-PG70-treated mice demonstrated a shift from a pro-inflammatory to an anti-inflammatory/regulatory profile. DerG-PG70 peptide tetramers preferentially bound to CD4+ T-cells of GIA spleen cells. We conclude that the DerG-PG70 vaccine (now designated CEL-4000) exerts its therapeutic effect by interacting with CD4+ cells, which results in an antigen-specific down-modulation of pathogenic T-cell responses in both the PGIA and GIA models of RA. Future studies will need to determine the potential of LEAPS vaccination to provide disease suppression in patients with RA. |
| Databáze: | OpenAIRE |
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