Age-related changes in arthritis susceptibility and severity in a murine model of rheumatoid arthritis.
BACKGROUND
Rheumatoid arthritis (RA) most often begins in females in the fourth-fifth decade of their life, suggesting that the aging of the immune system (immunosenescence) has a major role in this disease. Therefore, in the present study, we sought to investigate the effect of age on arthritis susceptibility in BALB/c mice using the proteoglycan (PG)-induced arthritis (PGIA) model of RA.


RESULTS
We have found that young, 1-month-old female BALB/c mice are resistant to the induction of PGIA, but with aging they become susceptible. PG-induced T cell responses decline with age, whereas there is a shift toward Th1 cytokines. An age-dependent decrease in T cell number is associated with an increased ratio of the memory phenotype, and lower CD28 expression. Antigen-presenting cells shifted from macrophages and myeloid dendritic cells in young mice toward B cells in older mice. The regulatory/activated T cell ratio decreases in older mice after PG injections indicating impaired regulation of the immune response.


CONCLUSIONS
We conclude that immunosenescence could alter arthritis susceptibility in a very complex manner including both adaptive and innate immunities, and it cannot be determined by a single trait. Cumulative alterations in immunoregulatory functions closely resemble human disease, which makes this systemic autoimmune arthritis model of RA even more valuable.
Tarjanyi
Oktavia
O
Section of Molecular Medicine, Departments of Orthopedic Surgery, Biochemistry and Internal Medicine (Rheumatology), Rush University Medical Center, Chicago, Illinois 60612, USA.
Boldizsar
Ferenc
F
Section of Molecular Medicine, Departments of Orthopedic Surgery, Biochemistry and Internal Medicine (Rheumatology), Rush University Medical Center, Chicago, Illinois 60612, USA.|Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, 7643, Hungary.
Nemeth
Peter
P
Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, 7643, Hungary.
Mikecz
Katalin
K
Section of Molecular Medicine, Departments of Orthopedic Surgery, Biochemistry and Internal Medicine (Rheumatology), Rush University Medical Center, Chicago, Illinois 60612, USA.
Glant
Tibor T
TT
Section of Molecular Medicine, Departments of Orthopedic Surgery, Biochemistry and Internal Medicine (Rheumatology), Rush University Medical Center, Chicago, Illinois 60612, USA.