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Clonally expanded CD8 T cells in patients with polymyalgia rheumatica and giant cell arteritis
V M Martinez-Taboada1, J J Goronzy, C M Weyand
1Department of Medicine, Division of Rheumatology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Insights
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) may be linked to specific T cell changes. Age-related alterations in CD8 T cell receptor repertoires, particularly Jbeta gene usage, might predispose individuals to these conditions.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are inflammatory conditions primarily affecting individuals over 50.
- Both GCA and PMR share age dependence and HLA associations, suggesting underlying immune system dysregulation.
- The role of T cell receptor (TCR) repertoire changes in the pathogenesis of GCA and PMR remains unclear.
Purpose of the Study:
- To investigate whether age-related alterations in the T cell receptor repertoire contribute to the risk of developing GCA and PMR.
- To analyze the diversity and characteristics of peripheral blood CD8+ T cells in patients with GCA and PMR.
Main Methods:
- Analysis of peripheral blood CD8+ T cell receptor repertoire diversity in untreated PMR/GCA patients and age-matched healthy controls.
- Molecular analysis of CD8+ clonotypes, including Vbeta and Jbeta gene segment usage.
- Assessment of T cell clonality persistence in relation to disease activity.
Main Results:
- Patients with PMR/GCA exhibited multiple clonally expanded CD8+ T cell populations.
- A restricted T cell receptor repertoire with distinct Jbeta gene segment usage was observed in patients compared to controls.
- Specific Jbeta2.7+ CD8+ clonotypes were exclusively found in patients, and oligoclonality persisted even after disease control.
Conclusions:
- The findings suggest that specific CD8+ T cells, potentially through a Jbeta-specific mechanism, play a functional role in the pathogenesis of GCA and PMR.
- Age-related changes in the CD8 T cell receptor repertoire composition, including the emergence of specific clonotypes, may predispose individuals to GCA and PMR.
- These T cell alterations are likely not merely a consequence of inflammation but may represent a predisposing factor.
Abstract:
Giant cell arteritis (GCA) is a vasculitic entity which exclusively, affects individuals older than 50 years of age. Polymyalgia rheumatica (PMR) is a closely related condition which lacks clinically significant vasculitic lesions but shares with GCA the age dependence and the HLA association. To examine whether age-related changes in the T cell receptor repertoire represent a risk factor in these two diseases, we have analyzed the diversity of peripheral blood CD8+ T cells. Untreated PMR/GCA patients carried multiple clonally expanded CD8 populations. The frequency of clonal expansion was not different from age-matched healthy controls. Molecular analysis of the CD8+ clonotypes showed a restricted repertoire in the patients with a distinct Jbeta gene segment usage compared to normal controls. Jbeta2.7+ CD8+ clonotypes were exclusively found in patients. Further evidence for selective CD8 cell expansion came from the finding that multiple clonotypes in the same patient transcribed identical Jbeta segments despite diversity of the Vbeta element. Oligoclonality in the CD8 repertoire persisted despite successful control of the disease activity, suggesting that the CD8+ clonotypes are not an epiphenomenon of the inflammation. We propose that selected CD8+ cells are of functional importance in the pathogenesis of GCA and PMR through a Jbeta-specific mechanism. Age-related changes in the composition of the CD8 T cell receptor repertoire with the emergence of such clonotypes may predispose individuals to develop PMR/GCA.