Related Experiment Videos
Rheumatoid arthritis.
Jörg J Goronzy1, Cornelia M Weyand
1Department of Medicine, Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory School of Medicine, Atlanta, GA 30322, USA. jgoronz@emory.edu
Immunological Reviews
|March 26, 2005
Summary
Immune system aging (immunosenescence) may be a key risk factor for rheumatoid arthritis (RA). Degenerate T cells accumulate in RA, driving chronic inflammation and disease onset, particularly in older adults.
Area of Science:
- Immunology
- Rheumatology
- Gerontology
Background:
- Rheumatoid arthritis (RA) pathogenesis involves adaptive immunity, yet RA affects elderly individuals with declining adaptive immunity.
- Immunosenescence, or immune system aging, is proposed as a risk factor for RA.
- Chronic inflammation in RA may stem from accumulated degenerate T cells with altered activation thresholds.
Purpose of the Study:
- To investigate the role of immunosenescence as a risk factor for rheumatoid arthritis (RA).
- To explore the characteristics of senescent T cells in RA patients.
- To understand the contribution of the synovial microenvironment to RA pathogenesis in the context of aging immunity.
Main Methods:
- Analysis of T cell populations in rheumatoid arthritis patients.
- Characterization of T cell surface markers, including CD28, KIR2DS2, NKG2D, and CX(3)CR1.
- Examination of the synovial microenvironment for features of immune response, such as ectopic lymphoid neogenesis.
Main Results:
- Immunosenescence is accelerated in RA and precedes disease onset, partly due to the HLA-DR4 haplotype.
- Senescent CD4(+) T cells in RA exhibit CD28 loss and express novel costimulatory receptors (KIR2DS2, NKG2D, CX(3)CR1), lowering activation thresholds.
- The RA synovial microenvironment supports chronic inflammation via ectopic lymphoid neogenesis and activation of senescent T cells.
Conclusions:
- Immune system aging is a significant risk factor for rheumatoid arthritis.
- Accumulation and altered function of senescent T cells in RA contribute to disease pathogenesis.
- The synovial environment exacerbates RA by promoting responses from aged immune cells.