Increased prevalence of activated CD70+CD4+ T cells in the periphery of patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance. A hallmark of SLE is the presence of autoantibodies resulting from B cell hyperactivity. Previous studies have shown that the presence of abnormal B cell subsets in the periphery, such as CD27highCD20- B cells, correlate with disease activity. We examined the relationship between the expression of CD70, the ligand for CD27 expressed by activated T cells, and indicators of disease activity. A significant increase in median CD70+CD4+ T cell frequencies and memory CD45RA-CD4+ T cell frequencies was observed in SLE samples as compared to healthy controls. The frequencies of CD70+CD4+ T cells correlated with disease duration but not age, treatment, or disease activity. Although a majority of CD70+CD4+ T cells appeared to be effector memory cells, mitogen-stimulated CD70+CD4+ T cells were capable of secreting a full repertoire of effector cytokines. Despite the presence of activated CD4+ T cells, no increase in immunosenescent CD4+ T cells, as defined by the loss of CD28 and/or the acquisition of CD57 was observed in samples from SLE patients. These studies indicate that increased CD70 expression might serve as a useful marker of abnormal T cell activity in SLE.

Enhanced Phosphoinositide 3-Kinase δ Activity Is a Frequent Event in Systemic Lupus Erythematosus That Confers Resistance to Activation-Induced T Cell Death

“…SLE patients also showed a frequent defect in AICD that was corrected by inhibition of p110d. Activation of the PI3K/PKB pathway correlated with an increase in the proportion of CD4 + memory cells, a hallmark of murine and human SLE (7,8). These results point at enhanced p110d activity as a cause for the accumulation of long-lasting memory cells in SLE patients, because p110d inhibition corrected the apoptosis defects of activated/memory SLE T cells.…”

“…A common feature in murine and human SLE is the presence of increased numbers of autoreactive T and B cells and an accumulation of CD4 + memory cells (7,8). Autoreactive T cells support B cell-mediated production of autoantibodies that form immune complexes; autoreactive SLE T and B lymphocytes affect a variety of organs, including skin, brain, and kidney (9).…”

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

“…CD70 overexpression is not only seen in RA patients; it has also been described in SLE (29,48). The mechanisms are different, but the functional consequences appear to be very similar.…”

Inhibition of PI3Kδ Reduces Kidney Infiltration by Macrophages and Ameliorates Systemic Lupus in the Mouse

“…Current immunosuppressive therapy based on long-term corticosteroid treatment presents side effects (4,5); it is thus important to develop therapeutic approaches that are more specific. In both human and murine lupus, autoreactive B and T cell numbers are increased, and there is accumulation of long-lasting CD4 + memory cells, which include the autoreactive T cells responsible for disease maintenance throughout life (6)(7)(8).…”