CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity.

Abstract

Clonal expansion of CD4ϩ T cells is a characteristic finding in patients with RA and is only infrequently found in patients with psoriatic arthritis and healthy controls. Expanded CD4ϩ clonotypes are present in the blood, infiltrate into the joint, and persist over years. We have now addressed the question of whether the expanded clonotypes have unique functional and phenotypic properties which may explain the preferential in vivo expansion in RA. In contrast to most CD4 ϩ T cells, expanded clonotypes lacked the expression of the CD28 and CD7 cell surface molecules. Accordingly, the subsets of CD4 ϩ CD28 Ϫ (9.7 vs. 1.7, P ϭ 0.00002) and CD4 ϩ CD7 Ϫ T cells (21.5 vs. 12.6, P ϭ 0.018) were increased in RA patients compared with age-matched normal individuals. Despite the lack of CD28 expression, clonally expanded CD4 ϩ T cells were not anergic but proliferated in response to immobilized anti-CD3 and could be maintained in tissue culture. In vivo expanded CD4 ϩ T cells were autoreactive to ubiquitously distributed autoantigens. They responded in an autologous mixed lymphocyte reaction, and T cell clones isolated from selected patients proliferated to autologous peripheral blood adherent cells. These data suggest that in RA patients selected CD4 ϩ T cells which share the CD7 Ϫ CD28 Ϫ phenotype escape from peripheral tolerance. ( J. Clin. Invest. 1996. 97

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

“…More significantly, CD8ϩ,CD56ϩ T cells tended to have a higher degree of representation of specific TCR AV and BV chains than CD4ϩ,CD56ϩ T cells ( Figure 3B). Patients had varying patterns of TCR expansion, consistent with studies indicating that T cell oligoclonality in RA may not be associated with any particular antigen (1)(2)(3)(4)(5).…”

Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis

“…A series of studies has established that the immune system of RA patients is prematurely aged (43). The remodeled T cell pool is filled with end-differentiated senescent memory T cells (44). Such T cells have altered tissue trafficking (45), are biased toward proinflammatory action, and preferentially interact with mesenchymal cells, such as synovial fibroblasts, in peripheral tissues (46).…”

CD57+/CD28− T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis

“…41 Peripheral CD4 + CD28 − T cells and/or T cell clones from patients with rheumatoid arthritis and type I diabetes are autoreactive, ie they respond to autologous antigen-presenting cells in the absence of antigen. 41,42 Furthermore, both autoimmunity and extreme expansions of peripheral CD4 + CD57 + T cells prevail in higher percentages in B-CLL patients with advanced disease stages than in patients with early stages. 39,43 Finally, autoimmune disorders are being recognized with increasing frequency in patients with HCL, 44 and have also been associated with NHL 45 but not with CML.…”