Clonally expanded CD8 T cells in patients with polymyalgia rheumatica and giant cell arteritis.
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.
Martinez-Taboada
V M
VM
Department of Medicine, Division of Rheumatology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Goronzy
J J
JJ
Weyand
C M
CM
D000368:Aged; D000595:Amino Acid Sequence; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002999:Clone Cells; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D013700:Giant Cell Arteritis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011111:Polymyalgia Rheumatica / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics
D016693:Receptors, Antigen, T-Cell, alpha-beta