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The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE210539 | GEO | 2023/04/06

REPOSITORIES: GEO

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The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (ATAC-Seq)

Project description:T-cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these memory-like CD8 T cell (CD8ML) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection we identify the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8ML as well as for virus control. IL-33 receptor- (ST2-) deficient CD8 T cells exhibit biased end-differentiation and premature loss of Tcf-1. Intriguingly, ST2-deficient CD8ML responses are restored by blockade of type I interferon signaling, suggesting that opposing IFN-I and IL-33 effects control CD8ML formation in chronic infection. IL-33 signals broadly augment chromatin accessibility in CD8ML and determine these cells’ re-expansion potential. Our study identifies the IL-33 – ST2 axis as an important CD8ML-promoting pathway in the context of chronic viral infection.

2023-04-06 | GSE210536 | GEO

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq I)

2023-04-06 | GSE210537 | GEO

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq II)

2023-04-06 | GSE210538 | GEO

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection

Project description:The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection

| PRJNA866121 | ENA

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (ATAC-Seq)

Project description:The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (ATAC-Seq)

| PRJNA866124 | ENA

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq I)

Project description:The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq I)

| PRJNA866123 | ENA

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq II)

Project description:The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq II)

| PRJNA866122 | ENA

The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses

Project description:Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as “damage-associated molecular patterns” or “alarmins”, remains ill-defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8+ T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a MyD88-dependent, CTL-intrinsic fashion, determined polyfunctional effector cell differentiation and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses. 2 groups (wt vs. ST-/- P14 cells), 3 replicates per group.

2012-02-27 | E-GEOD-34392 | biostudies-arrayexpress

The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses

2012-02-27 | GSE34392 | GEO

TCF-1 regulates HIV-specific CD8+ T cell expansion capacity.

Project description:Although many HIV cure strategies seek to expand HIV-specific CD8+ T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus-specific CD8+ T cells. We found that virus-specific CD8+ T cells from humans and nonhuman primates naturally controlling HIV/SIV infection express more of the transcription factor TCF-1 than noncontrollers. HIV-specific CD8+ T cell TCF-1 expression correlated with memory marker expression and expansion capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 contributes to the regulation of the stem-like memory property of secondary expansion capacity of HIV-specific CD8+ T cells, and they provide a rationale for exploring the enhancement of this pathway in T cell-based therapeutic strategies for HIV.

| S-EPMC7934879 | biostudies-literature

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