Interleukin-17+CD8+ T Cells Are Enriched in the Joints of Patients With Psoriatic Arthritis and Correlate With Disease Activity and Joint Damage Progression

Psoriatic arthritis (PsA) is an inflammatory joint disease of unclear etiology that affects ∼10–30% of patients with the skin condition psoriasis (1). Although PsA, like rheumatoid arthritis (RA), can result in pain, loss of function, and damage of the joint, the disease is clinically, radiologically, and serologically distinct from RA (2–4). In addition, PsA and RA have different genetic associations with the major histocompatibility complex region that encodes HLA, in which RA is associated with HLA class II, whereas PsA is associated with HLA class I (5–7). These differences suggest that the immunopathologic mechanisms of these 2 diseases may also differ. The association with HLA class I suggests that CD8+ T cells have a role in the pathogenesis of PsA. This is supported by observational data; patients with advanced human immunodeficiency virus (HIV) status and low CD4+ T cell counts may develop de novo or worsening PsA and/or psoriasis, whereas patients with CD4+ T cell–driven diseases such as RA have shown improvement at the onset of HIV infection (8,9). It has been suggested that the corresponding increase in memory CD8+ T cells, comprising up to 80% of the total T cell compartment in severe HIV infection, contributes to the development of PsA in this context (10). Despite the suggestions that CD8+ T cells play an important role in the pathogenesis of PsA (11,12), most studies of T cell cytokine expression in PsA have focused on CD4+ T cells, particularly those expressing the proinflammatory cytokines interleukin-17A (IL-17A), interferon-γ (IFNγ), or tumor necrosis factor α (TNFα) (13–15). The proinflammatory cytokine IL-17 is of particular interest because of its potent osteoclastogenic activity and its ability to up-regulate matrix metalloproteinases and proinflammatory cytokines (IL-1β, IL-8, TNFα) (16). We previously showed that levels of synovial IL-17 messenger RNA (mRNA), in synergy with TNFα, are predictive of joint damage progression in RA (17), and that the percentage of synovial IL-17–producing CD4+ T cells is correlated with markers of disease activity and active synovitis in RA (18). IL-17+CD4+ T cells have been studied in patients with PsA (13,14,19,20); however, the role of IL-17+CD8+ T cells in the PsA joint is currently unknown. Herein we present a detailed investigation of the presence of IL-17+ T cells and other cytokine-expressing T cells (CD4+ versus CD4− T cells) in the peripheral blood (PB) and synovial fluid (SF) of patients with PsA. Our findings show that IL-17+CD4− T cells are predominantly CD8+ cells, and their levels are significantly increased in the SF of patients with PsA. Moreover, the levels of these cells are significantly correlated with measures of disease activity, the erosion status assessed by radiography, and the presence of active synovitis assessed by power Doppler ultrasonography (PDUS). Our data suggest that IL-17–producing CD8+ T cells may constitute an as-yet-unrecognized pathogenic immune cell population in patients with PsA.