Decreased effector memory CD45RA+ CD62L- CD8+ T cells and increased central memory CD45RA- CD62L+ CD8+ T cells in peripheral blood of rheumatoid arthritis patients

Abstract

Although a role for CD8+ T cells in the pathogenesis of rheumatoid arthritis (RA) has been suggested, the precise nature of their involvement is not fully understood. In the present study we examined the central and effector memory phenotypes of CD4+ and CD8+ T cells in the peripheral blood of patients with RA and systemic lupus erythematosus. Terminally differentiated effector memory CD45RA+CD62L-CD8+ T cells were significantly decreased in RA patients, whereas the central memory CD45RA-CD62L+ CD8+ T-cell population was increased as compared with levels in healthy control individuals. Naïve and preterminally differentiated effector memory CD45RA-CD62L- CD8+ T cells did not differ between RA patients and control individuals. The CD45RA-CD62L+ central memory CD4+ T-cell subpopulation was increased in RA patients, whereas the naïve and effector memory phenotype of CD4+ T cells did not differ between RA patients and control individuals. In patients with systemic lupus erythematosus the distribution of naïve/memory CD4+ and CD8+ T cells did not differ from that in age- and sex-matched control individuals. These findings show that peripheral blood CD8+ T cells from RA patients exhibit a skewed maturation phenotype that suggests a perturbation in the homeostasis of these cells. The central memory CD45RA-CD62L+ CD4+ and CD8+ T-cell numbers were increased in RA, suggesting an accelerated maturation of naïve T cells. The decreased numbers of terminally differentiated CD45RA+CD62L- effector memory CD8+ T cells in peripheral blood of RA patients may reflect increased apoptosis of these cells or enhanced migration of these cells to sites of inflammation, which may play a role in the pathogenesis of RA.

Figure 1

Naïve and memory CD4⁺ and CD8⁺ T-cell subpopulations in patients with rheumatoid arthritis (RA), patients with systemic lupus erythematosus (SLE), and healthy control individuals. (a) Representative flow cytometry showing naïve and memory subpopulations of CD4⁺ and CD8⁺ T cells from one RA patient and a sex- and age-matched control individual. (b) Pooled data showing naïve and memory subpopulations of CD4⁺ and CD8⁺ T cells from RA patients (n = 8) and control individuals (n = 8). Horizontal lines indicate means. (c) Pooled data showing naïve and memory subpopulations of CD4⁺ and CD8⁺ T cells from SLE patients (n = 12) and control individuals (n = 12). Horizontal lines indicate means. (d) The correlation between age and CD45RA⁺CD62L^- terminally differentiated CD8⁺ T cells from control individuals (n = 13), RA patients (n = 8), and SLE patients (n = 12) is shown. The P values were calculated using Mann–Whitney U test and Student's t-test for panel b and linear regression for panel d.

Figure 2

Representation of skewed CD8⁺ T-cell phenotype in patients with rheumatoid arthritis (RA) as compared with sex- and age-matched healthy control individuals, indicating the relative sizes of the different naïve and memory populations of CD8⁺ T cells. Percentages refer to the proportions of different naïve/memory population of total CD8⁺ T cells.