Dysregulated interferon γ and interleukin 2 synthesis in peripheral blood T cells in quiescent systemic lupus erythematosus is dependent on the affected T cell receptor ζ chain expression

Szmyrka, Magdalena; Ciszak, Lidia; Węglarz, Mateusz; Andrzejewska, Karolina; Wiland, Piotr; Kosmaczewska, Agata

doi:10.20452/pamw.4337

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“…In our previous reports, we showed that immunological alterations, including impaired TCRζ chain expression affecting T helper (Th) type 1 (Th1) cytokines expression and Th17/Treg imbalance, might precede clinical and laboratory indices of SLE flares. 17,18 The current study extends our attention to determining the relevance of the level of CD28 expression for CD4 + T-cell effector function in SLE, especially since the phenotypic and functional characteristics of CD4 + CD28 null T cells suggest that they might be pathogenic cells in autoimmune disorders. 6,19–27 There is still a lack of studies on the impact of CD28 expression on the function of circulating CD4 + T cells in SLE in different clinical courses.…”

Section: Discussionmentioning

confidence: 65%

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

Kosmaczewska

Ciszak

Stosio

et al. 2020

Lupus

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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.

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Section: Discussionmentioning

confidence: 65%

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

Kosmaczewska

Ciszak

Stosio

et al. 2020

Lupus

Self Cite

View full text Add to dashboard Cite

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Dysregulated interferon γ and interleukin 2 synthesis in peripheral blood T cells in quiescent systemic lupus erythematosus is dependent on the affected T cell receptor ζ chain expression

Cited by 1 publication

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

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

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Dysregulated interferon γ and interleukin 2 synthesis in peripheral blood T cells in quiescent systemic lupus erythematosus is dependent on the affected T cell receptor ζ chain expression

Cited by 1 publication

References 0 publications

CD4+CD28nullT cells are expanded in moderately active systemic lupus erythematosus and secrete pro-inflammatory interferon gamma, depending on the Disease Activity Index

CD4+CD28nullT cells are expanded in moderately active systemic lupus erythematosus and secrete pro-inflammatory interferon gamma, depending on the Disease Activity Index

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

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