Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes

Abstract

Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann-Whitney test. Bonferroni correction was applied to adjust for multiple comparisons ( p). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls ( p = .04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K ≥ 6 ( n = 13) had a higher percentage of circulating CD4+ T-cells with CD28- phenotype ( p= .005) as well as those with an effector memory ( p= .004) and TDEM ( p= .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02), in comparison with patients with low disease activity ( n = 38). Patients with damage (SDI ≥ 1) tended to show an expansion of TDEM among CD4+ T-cells as compared with patients with no damage ( p = .01). In SLE patients an inverse correlation was found between the percentages of TREGs and those of TDEM ( p < .01) or CD4 + CD28- ( p < .01) T-cells. Conclusions CD4+ T-cell subpopulations displaying phenotype characteristics of effector lymphocytes are proportionally expanded in patients with active SLE and a higher damage index. These findings may suggest a role of effector T-cells in the pathogenesis of the disease and in the mechanisms of damage in SLE.

Association of Platelet Binding to Lymphocytes with B Cell Abnormalities and Clinical Manifestations in Systemic Lupus Erythematosus

“…We and others have shown that platelet bound preferably to memory T lymphocytes [19, 46]. Therefore, the described expansion of memory and effector T lymphocytes in SLE patients [47] could explain the increased binding of platelets to SLE than to HD lymphocytes. Several pairs of molecules, such as PSGL-1-P-selectin, have been shown to be involved in the lymphocyte-platelet complex formation in HD.…”

The IMMENSE Study: The Interplay Between iMMune and ENdothelial Cells in Mediating Cardiovascular Risk in Systemic Lupus Erythematosus

“…The inverse correlation of T ang cells with disease activity suggests that SLE-specific mechanisms could mediate the deterioration of this T cell subset. This should not be surprising, as immunosenescence might be driven not only by aging but also by repeated antigen stimulations as happens in systemic autoimmune diseases such as SLE (42). Besides the loss of CD28, several additional processes occur, influencing the number and function of circulating immune cells, such as telomere attrition and DNA damage (43).…”

Inhibition of miR-22-3p reduces kidney disease associated with systemic lupus erythematosus

“…Due to the observed reduction in markers of SLE by LNA-22 treatments, we sought to determine if this was due to a reduction in immune cell activation. During lupus, T cell abnormalities include T cell hyperactivation, accumulation of effector memory T cells (CD44 hi CD62L lo ), as well as increased IFN-g production [41]. T EM cells, which can stimulate cytokine production rapidly following migration to inflamed tissues in SLE [42], were significantly reduced following LNA-22 treatment in SLE mice.…”