ABSTRACT
The study was aimed to investigate whether quantities of CD8(+) T cell subsets are normal in juvenile idiopathic arthritis (JIA) patients with disease remission compared to age-matched healthy donors (HD) and whether chronological age may have an impact on proportions of naive CD8(+) T cells. CD8(+) T cell subsets were analyzed in 17 JIA patients and 32 age-matched HD by flow cytometry. JIA patients showed lower CD3(+)CD8(+) T cells compared to HD. Total counts of CD8(+)CD28(+) and CD8(+)CD28(+)CD45RA(+) T cells were inversely correlated to chronological age in JIA patients and HD. In JIA patients, percentages of CD8(+)CD28(+)CD45RA(+) T cells and of CD62L-expressing CD8(+)CD28(+)CD45RA(+) T cells showed a negative correlation with age. The trend to lower CD28(+)CD45RA(+) T cell proportions in aged JIA patients in remission may reflect a disturbed T cell homeostasis independently of disease activity and may be due to an intrinsic effect in reconstitution of the peripheral T cells.
Subject(s)
Arthritis, Juvenile/blood , Arthritis, Juvenile/therapy , CD8-Positive T-Lymphocytes/metabolism , Adolescent , Age Factors , Arthritis, Juvenile/pathology , CD28 Antigens/biosynthesis , Child , Child, Preschool , Female , Humans , L-Selectin/biosynthesis , Leukocyte Common Antigens/biosynthesis , Lymphocyte Subsets , Male , Remission Induction , Treatment OutcomeABSTRACT
OBJECTIVE: Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence. METHODS: To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation. RESULTS: JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67-positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04). CONCLUSION: Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.
Subject(s)
Aging/immunology , Arthritis, Juvenile/immunology , Ki-67 Antigen/biosynthesis , T-Lymphocytes/immunology , Case-Control Studies , Child , Female , Gene Expression , Humans , Lymphocyte Count , MaleABSTRACT
OBJECTIVE: To investigate the influence of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on CD28-expressing T-cell subpopulations and replicative senescence of naive T-cells as a marker for aging of the immune system in children with juvenile ideopathic arthritis (JIA). METHODS: T-cell subpopulations were analyzed from 24 patients with JIA and 61 healthy age-matched controls by fluorescence activated cell sorting. Relative telomere length (RTL) in CD4+CD28+CD45RA+ (naive) T-cells was measured by quantitative polymerase chain reaction. RESULTS: Although confirming known data of expansions of CD28- T-cells and tendency of decreasing naive T-cells in CMV-seropositive healthy individuals, our findings did not show a marked influence of latent EBV or CMV infection on CD28-expressing T-cells in patients with JIA. In contrast, CMV was an independent factor for loss of CD28, regardless of age, in healthy controls. Irrespective of serology results for CMV or EBV, patients with JIA showed signficantly decreased RTL compared to age-matched controls. Regression lines for RTL and age revealed decreased RTL with advancing age in CMV-positive and EBV-positive subjects. The evidence that findings for CMV-positive JIA patients did not resemble the findings of healthy CMV-positive controls, namely expansion of CD28- T-cells and decrease of naive T-cells, may support the theory of a disturbed peripheral T-cell homeostasis in JIA. CONCLUSION: Diminished mechanisms of T-cell homeostasis and premature aging of the immune system may play a role in the pathogenesis of JIA.
