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Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon

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

ORGANISM(S): Mus musculus

PROVIDER: GSE178449 | GEO | 2021/06/19

REPOSITORIES: GEO

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Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [Array]

Project description:The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise role, functional relationship, and underlying mechanisms have not been elucidated completely. Here, we demonstrate that naive CD8+ T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon (T1IFN), resulting in three distinct subsets, CD5loLy6C–, CD5hiLy6C–, and CD5hiLy6C+ cells. CD5hiLy6C+ cells differ from CD5loLy6C– and CD5hiLy6C– cells in their gene expression profiles and functional properties. Moreover, CD5hiLy6C+ cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such unique features of CD5hiLy6C+ cells are imprinted in a steady-state and observed even for those of monoclonal CD8+ T cell populations in a T1IFN dependent fashion. These findings demonstrate that self-reactivity shapes the functional diversity of naive CD8+ T cells by co-opting tonic T1IFN signaling.

2021-06-19 | GSE178445 | GEO

Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [RNA-Seq_2]

2021-06-19 | GSE178448 | GEO

Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [RNA-Seq_1]

2021-06-19 | GSE178447 | GEO

Self-reactivity controls functional diversity of naive CD8<sup>+</sup> T cells by co-opting tonic type I interferon.

Project description:The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise function and underlying mechanisms are unclear. Here, we demonstrate that naive CD8+ T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon, resulting in three distinct subsets, CD5loLy6C-, CD5hiLy6C-, and CD5hiLy6C+ cells. CD5hiLy6C+ cells differ from CD5loLy6C- and CD5hiLy6C- cells in terms of gene expression profiles and functional properties. Moreover, CD5hiLy6C+ cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such features of CD5hiLy6C+ cells are imprinted in a steady-state and type I interferon dependence is observed even for monoclonal CD8+ T cell populations. These findings demonstrate that self-reactivity controls the functional diversity of naive CD8+ T cells by co-opting tonic type I interferon signaling.

| S-EPMC8523551 | biostudies-literature

Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon

Project description:Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon

| PRJNA739103 | ENA

Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [Array]

Project description:Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [Array]

| PRJNA739107 | ENA

Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [RNA-Seq_1]

Project description:Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [RNA-Seq_1]

| PRJNA739108 | ENA

Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [RNA-Seq_2]

Project description:Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [RNA-Seq_2]

| PRJNA739109 | ENA

Heightened self-reactivity associated with selective survival, but not expansion, of naive virus-specific CD8+ T cells in aged mice.

Project description:In advanced age, decreased CD8(+) cytotoxic T-lymphocyte (CTL) responses to novel pathogens and cancer is paralleled by a decline in the number and function of naïve CTL precursors (CTLp). Although the age-related fall in CD8(+) T-cell numbers is well established, neither the underlying mechanisms nor the extent of variation for different epitope specificities have been defined. Furthermore, naïve CD8(+) T cells expressing high levels of CD44 accumulate with age, but it is unknown whether this accumulation reflects their preferential survival or an age-dependent driver of CD8(+) T-cell proliferation. Here, we track the number and phenotype of four influenza A virus (IAV)-specific CTLp populations in naïve C57BL/6 (B6) mice during aging, and compare T-cell receptor (TCR) clonal diversity for the CD44hi and CD44lo subsets of one such population. We show differential onset of decline for several IAV-specific CD8(+) T-cell populations with advanced age that parallel age-associated changes in the B6 immunodominance hierarchy, suggestive of distinct impacts of aging on different epitope-specific populations. Despite finding no evidence of clonal expansions in an aged, epitope-specific TCR repertoire, nonrandom alterations in TCR usage were observed, along with elevated CD5 and CD8 coreceptor expression. Collectively, these data demonstrate that naïve CD8(+) T cells expressing markers of heightened self-recognition are selectively retained, but not clonally expanded, during aging.

| S-EPMC4747731 | biostudies-literature

Cross-Reactivity with Self-Antigen Tunes the Functional Potential of Naive B Cells Specific for Foreign Antigens.

Project description:Upon Ag exposure, naive B cells expressing BCR able to bind Ag can undergo robust proliferation and differentiation that can result in the production of Ab-secreting and memory B cells. The factors determining whether an individual naive B cell will proliferate following Ag encounter remains unclear. In this study, we found that polyclonal naive murine B cell populations specific for a variety of foreign Ags express high levels of the orphan nuclear receptor Nur77, which is known to be upregulated downstream of BCR signaling as a result of cross-reactivity with self-antigens in vivo. Similarly, a fraction of naive human B cells specific for clinically-relevant Ags derived from respiratory syncytial virus and HIV-1 also exhibited an IgMLOW IgD+ phenotype, which is associated with self-antigen cross-reactivity. Functionally, naive B cells expressing moderate levels of Nur77 are most likely to proliferate in vivo following Ag injection. Together, our data indicate that BCR cross-reactivity with self-antigen is a common feature of populations of naive B cells specific for foreign Ags and a moderate level of cross-reactivity primes individual cells for optimal proliferative responses following Ag exposure.

| S-EPMC6981075 | biostudies-literature

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