CD4⁺CD28^null T cells are expanded in moderately active systemic lupus erythematosus and secrete pro-inflammatory interferon gamma, depending on the Disease Activity Index

Abstract

Background Pathogenic CD4+CD28null cells are characterized by inflammatory cytokine synthesis and tropism to the inflamed tissues. Recent studies showed the involvement of CD28null T cells in a severe clinical outcome of lupus. However, their role in moderately active disease is still unresolved. Methods We examined the levels of circulating CD4+CD28null cells and CD8+CD28null suppressor T cells. We also compared the CD4+CD28null and CD4+CD28+ T-cell functional properties, including the expression of interferon gamma (IFN-γ) and Ki67 among systemic lupus erythematosus (SLE) patients ( n = 20) and healthy controls ( n = 20). All the patients were under immunosuppressive treatment and exhibited moderate SLE activity (median SLE Disease Activity Index (SLEDAI) = 6). Results In patients, we found elevated CD4+CD28null and unchanged levels of suppressor CD8+CD28null T cells. There was no difference between patients and controls in IFN-γ and Ki67-expressing CD4+, CD4+CD28+, and CD4+CD28null T cells, except for higher IFN-γ levels in CD4+CD28+ T cells in SLE. In each studied group, we observed a higher preponderance of IFN-γ- and Ki67-expressing cells among CD4+CD28null T cells and lower levels of IFN-γ in CD4+CD28null T cells compared to the CD28+ subset. Similarly, Ki67 intensity was decreased in healthy CD4+CD28null cells, whereas in patients, comparably high expression was observed in both subsets. IFN-γ intensity in CD4+CD28null T cells correlated with SLEDAI. Conclusion SLE with a moderately active clinical course is characterized by peripheral blood expansion of CD4+CD28null T cells and a normal abundance of suppressor CD8+CD28null T cells. The demonstration that these pathogenic CD4+ T cells, despite the lack of CD28, maintain the ability to produce pro-inflammatory IFN-γ positively correlated with disease activity as well as relatively high proliferative capacity may suggest their potentially predictive role in SLE flares.

CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

“…This is comparable with past study demonstrating that untreated SLE patients had higher surface levels of gp130 on CD4 + T cells than inactive or stable SLE patients (47). Subsets of CD3 + CD4 + cells have been shown to be expanded in active SLE (48,49), and overactive or chronically active T cells are crucial in the pathogenesis of SLE (50,51). In addition, correlation with SLEDAI-2K scores was not observed in our cohort of patients when surface levels of IL-12Rb2 were taken into account i.e.…”

The Mango’s Mistletoe Leaves Extract Ameliorates Lupus by Inhibiting the Anti-dsDNA Antibody Production, the Percentages of CD8+CD28− and CD4+CD28− T Cells

“…− T cells CD4 + CD28 − T cells were utilized to predict damage in patients with SLE [1]. In this research, it was discovered that the positive control had a larger percentage of CD4 +…”

“…Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against diverse nuclear components that affect almost all internal organs and tissues and have a significant impact on patients' survival [1], [2]. Around the world, North America has the highest estimates of SLE incidence and prevalence (23.2/100,000 person/year and 241/100,000 people, respectively [3].…”

“…The CD8 + CD28+ T cell is a cytotoxic T lymphocyte population [12]. The loss of the CD28 molecule may be caused by a pro-inflammatory environment and repeated antigen stimulation [1]. If there is a repeated stimulation by the same antigen, it causes the progressive loss of CD28, eventually resulting in the formation of CD28 − T cells with shortened telomeres [10], [13].…”

T Cells in Autoimmunity-Associated Cardiovascular Diseases

“…A limited body of data also suggests a role for other T cell subsets in SLE-related CVD. CD4+CD28− T cells are expanded in SLE, but their relationship to atherogenesis is not well defined ( 118 ). Angiogenic T cells have also been described in the context of SLE; in contrast to RA, SLE is typified by expansion of angiogenic CD8+ cells but not angiogenic CD4+ cells.…”