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

• Published in: Lupus 2020-06, Vol.29 (7), p.705-714
• Main Authors: Kosmaczewska, Agata, Ciszak, Lidia, Stosio, Malgorzata, Szteblich, Aleksandra, Madej, Marta, Frydecka, Irena, Wiland, Piotr, Szmyrka, Magdalena
• Format: Article
• Language: English
• Subjects: Adult; Case-Control Studies; CD28 Antigens - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes; Female; Flow Cytometry; Humans; Interferon-gamma - immunology; Lupus Erythematosus, Systemic - immunology; Male; Middle Aged; Severity of Illness Index
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203320917749

Pathogenic CD4 CD28 cells are characterized by inflammatory cytokine synthesis and tropism to the inflamed tissues. Recent studies showed the involvement of CD28 T cells in a severe clinical outcome of lupus. However, their role in moderately active disease is still unresolved. We examined the levels of circulating CD4 CD28 cells and CD8 CD28 suppressor T cells. We also compared the CD4 CD28 and CD4 CD28 T-cell functional properties, including the expression of interferon gamma (IFN-γ) and Ki67 among systemic lupus erythematosus (SLE) patients (  = 20) and healthy controls (  = 20). All the patients were under immunosuppressive treatment and exhibited moderate SLE activity (median SLE Disease Activity Index (SLEDAI) = 6). In patients, we found elevated CD4 CD28 and unchanged levels of suppressor CD8 CD28 T cells. There was no difference between patients and controls in IFN-γ and Ki67-expressing CD4 , CD4 CD28 , and CD4 CD28 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 CD28 T cells and lower levels of IFN-γ in CD4 CD28 T cells compared to the CD28+ subset. Similarly, Ki67 intensity was decreased in healthy CD4 CD28 cells, whereas in patients, comparably high expression was observed in both subsets. IFN-γ intensity in CD4 CD28 T cells correlated with SLEDAI. SLE with a moderately active clinical course is characterized by peripheral blood expansion of CD4 CD28 T cells and a normal abundance of suppressor CD8 CD28 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.