Introduction
Systemic lupus erythematosus (SLE) is an autoimmune, multifactorial disease with broad tissue and organ involvement. Its manifestations are usually heterogeneous, with a fluctuating and unpredictable course [1]. Despite the advances in the treatment and understanding of its pathogenesis, disease activity continues to be one of the major causes of morbidity and mortality. Progressive accumulation of irreversible damage is attributed to chronic inflammation, as well as to the prolonged use of steroids and immunosuppressants [2]. Many studies conducted in recent years have focused on the search for treatments and interventions that reduce or prevent relapses in patients with SLE, with the goal of reaching a sustained remission and limiting damage [3, 4]. Despite the information provided by these studies, very little is known about the clinical and serological features that characterize the group of patients with SLE who achieve sustained remission and the cellular, genetic, or molecular factors involved in this task.
T-cell exhaustion is a complex process that has been increasingly recognized in recent years in patients with chronic infections and cancer. T-cell exhaustion is driven by persistent TCR stimulation in the absence of enough co-stimulation and is characterized by limited proliferation, cytokine production, and effector function [5]. There is not a universally accepted set of markers that define the population of exhausted T cells, however, is recognized that they express a variety of inhibitory receptors that reduce their response after activation, such as PD-1, Tim-3 or 2B4 and differentially express transcription factors such as EOMES and T-bet.
There are few reports about the role of exhausted T cells in autoimmunity, but they have linked their presence with an improved prognosis in several autoimmune diseases [6]. There is also evidence of an association of exhausted T cells and increased immune tolerance in transplantation [7]. Because of this potentially favorable effect of the exhaustion process in autoimmunity, we conducted this study with the aim of measuring CD4+ and CD8+ T cell exhaustion by quantifying surface inhibitory molecules and transcriptional factors by flow cytometry in SLE patients in prolonged remission and to compare them with active SLE patients and healthy subjects.
Material and Methods