Faculty Opinions recommendation of Sensor function for butyrophilin 3A1 in prenyl pyrophosphate stimulation of human vγ2vδ2 T cells.

Abstract Psoriasis is a frequent autoimmune-related skin disease, which involves various cell types such as T cells, keratinocytes and dendritic cells. Genetic variations, such as mutations of CARD14, can promote the development of the disease. CARD14 mutations as well as the stimulation of immune and cytokine receptors activate the paracaspase MALT1, a potent activator of the transcription factors NF-κB and AP-1. The disease-promoting role of MALT1 for psoriasis is mediated by both its protease activity as well as its molecular scaffold function. Here, we review the importance of MALT1-mediated signaling and its therapeutic implications in psoriasis.

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Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽

10.3390/v13081490 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1490

Author(s):

Victoria Matyushenko ◽

Irina Isakova-Sivak ◽

Igor Kudryavtsev ◽

Arina Goshina ◽

Anna Chistyakova ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Memory T Cells ◽

Natural Infection ◽

Intracellular Cytokine Staining ◽

T Cell Responses ◽

Effector Memory ◽

Memory T Cell ◽

Cell Responses ◽

Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

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Antigen-driven EGR2 expression is required for exhausted CD8+ T cell stability and maintenance

Nature Communications ◽

10.1038/s41467-021-23044-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mayura V. Wagle ◽

Stephin J. Vervoort ◽

Madison J. Kelly ◽

Willem Van Der Byl ◽

Timothy J. Peters ◽

...

Keyword(s):

T Cells ◽

Transcription Factor ◽

Cd8 T Cell ◽

Chronic Stimulation ◽

Epigenetic State ◽

Multiple Differentiation ◽

Cell Stability ◽

Substantial Interest ◽

Transcriptional State ◽

Stimulation Of

AbstractChronic stimulation of CD8+ T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Here, we show that chronic antigen induces the anergy-associated transcription factor EGR2 selectively within progenitor exhausted cells in both chronic LCMV and tumours. EGR2 enables terminal exhaustion and stabilizes the exhausted transcriptional state by both direct EGR2-dependent control of key exhaustion-associated genes, and indirect maintenance of the exhausted epigenetic state. We show that EGR2 is a regulator of exhaustion that epigenetically and transcriptionally maintains the differentiation competency of progenitor exhausted cells.

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