Selective T cell receptor decrease in peripheral blood T lymphocytes of patients with polymyalgia rheumatica and giant cell arteritis

Abstract

Objectives: To investigate the phenotype and T cell receptor (TCR) use in peripheral blood T cells in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Methods: Circulating T lymphocyte phenotype and TCR repertoire were studied by flow cytometry using specific monoclonal antibodies in 23 healthy controls and 37 patients with PMR/GCA. Results: Patients with active PMR/GCA showed an inverse relation between naive and memory CD4+ T cells and unchanged expression of activation surface markers compared with controls. CD4+ TCR BV expansions were seen in 12 (52%) controls and in 8 (22%) patients with active disease (p = 0.03). Within the CD8+ subset, the frequency of expansions was similar between groups. Most T cell expansions remained stable over time. Seventeen of the 23 patients with active PMR/GCA disclosed a simultaneous CD4+ and CD8+ T cell depletion for at least one particular BV family with a clear predominance of BV5S2/S3. Conclusions: The phenotype of circulating T cells in patients with PMR/GCA is similar to that found in aged healthy subjects, except for the surface markers of naive and memory cells and a striking non-activated phenotype. Specific BV expansions in CD4+ and CD8+ T cells, which remain stable over time, are frequent in aged subjects, including patients with PMR/GCA. TCR BV changes in patients with active disease seem to be also age related, except for the significant decrease in certain BV families in both CD4+ and CD8+ T cell subsets, which may favour the participation of a superantigen stimulation in PMR/GCA. G iant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two closely related syndromes affecting elderly people.1 GCA is a granulomatous vasculitis affecting medium and large sized arteries, and the inflammatory lesions are characterised by the presence of mononuclear cells, multinuclear giant cells, and fragmentation of the internal elastic laminae.

Serum Amyloid A as a Potent Therapeutic Marker in a Refractory Patient with Polymyalgia Rheumatica

“…Several reports have demonstrated that CD8 + T cells are decreased, and CD4 + and naive (CD4 + CD45RA + ) T cells are increased in the active phase of PMR on flow cytometry (18)(19)(20). The present patient also showed improvement of clinical symptoms in parallel with an increase in CD8 + CD25 + cells and a decrease in CD4 + CD25 + cells and CD4 + CD45RA + cells.…”

Pathogenesis of polymyalgia rheumatica

“…The same group demonstrated that the phenotype of circulating T-cells in patients with PMR/GCA is similar to that found in aged healthy subjects, except for the surface markers of naive and memory cells and a striking non-activated phenotype (55). In particular, Lopez-Hoyos and co-workers showed that specific TCR BV changes occur in patients with active disease accompanied by a significant decrease in certain TCRBV families in both CD4+ and CD8+ T-cell subsets, which may favour the participation of a superantigen stimulation in PMR/GCA (54). In both GCA and PMR patients, NKG2D was preferentially expressed on senescent CD4 CD28(-) and CD8 CD28(-), as well as on CD8 CD28 Tcells (55).…”

“…Molecular analysis of the CD8 + clonotypes showed a restricted TCR repertoire in the patients with a distinct Jbeta gene segment usage (54). 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 (54). The same group demonstrated that the phenotype of circulating T-cells in patients with PMR/GCA is similar to that found in aged healthy subjects, except for the surface markers of naive and memory cells and a striking non-activated phenotype (55).…”

“…The Authors demonstrated that untreated PMR/GCA patients carried multiple clonally expanded CD8 populations. Molecular analysis of the CD8 + clonotypes showed a restricted TCR repertoire in the patients with a distinct Jbeta gene segment usage (54). 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 (54).…”

An Uneven Expression of T Cell Receptor V Genes in the Arterial Wall and Peripheral Blood in Giant Cell Arteritis

“…Furthermore, a study by Lopez-Hoyos et al found simultaneous depletion in peripheral blood CD4+ and CD8+ subsets of certain TCR Vβ families, in particular Vβ 5.2-3 [45]. The authors speculated that their findings could be due to T cell encounter with a bacterial or viral superantigen, resulting in activation and proliferation of the majority of T cells bearing the particular Vβ element (a few of which could be autoreactive against vessel wall antigens), followed by depletion due to activationinduced cell death.…”