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