Signals for antigen-independent differentiation of memory CD8+ T cells

Kwesi-Maliepaard, Eliza Mari; Jacobs, Heinz; Leeuwen, Fred van

doi:10.1007/s00018-021-03912-9

Cited by 4 publications

(4 citation statements)

References 106 publications

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“…Innate CD8 T cells correspond to memory-phenotype (MP) CD8 T cells, whose generation is considered mostly cytokine-driven and not an antigen-driven event [31]. Depending on the anatomical location where these cells arise and the identity of the cytokine that drives their differentiation, several distinct populations of MP CD8 T cells have been proposed [32,33].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory IFNγ Is Produced by but Not Required for the Generation of Eomes+ Thymic Innate CD8 T Cells

Won,

Liman,

et al. 2023

Cells

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Innate CD8 T cells are proinflammatory effector T cells that achieve functional maturation in the thymus prior to their export into and maturation in peripheral tissues. Innate CD8 T cells produce the Th1 cytokine IFNγ but depend on the Th2 cytokine IL-4 for their generation. Thus, innate CD8 T cells can permute the intrathymic cytokine milieu by consuming a Th2 cytokine but driving a Th1 cytokine response. The cellular source of IL-4 is the NKT2 subset of invariant NKT (iNKT) cells. Consequently, NKT2 deficiency results in the lack of innate CD8 T cells. Whether NKT2 is the only iNKT subset and whether IL-4 is the only cytokine required for innate CD8 T cell generation, however, remains unclear. Here, we employed a mouse model of NKT1 deficiency, which is achieved by overexpression of the cytokine receptor IL-2Rβ, and assessed the role of other iNKT subsets and cytokines in innate CD8 T cell differentiation. Because IL-2Rβ-transgenic mice failed to generate both NKT1 and innate CD8 T cells, we postulated an in vivo requirement for IFNγ-producing NKT1 cells for innate CD8 T cell development. In-depth analyses of IL-2Rβ-transgenic mice and IFNγ-deficient mice, however, demonstrated that neither NKT1 nor IFNγ was required to induce Eomes or to drive innate CD8 T cell generation. Instead, in vivo administration of recombinant IL-4 sufficed to restore the development of innate CD8 T cells in NKT1-deficient mice, affirming that intrathymic IL-4, and not IFNγ, is the limiting factor and key regulator of innate CD8 T cell generation in the thymus.

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Section: Discussionmentioning

confidence: 99%

Proinflammatory IFNγ Is Produced by but Not Required for the Generation of Eomes+ Thymic Innate CD8 T Cells

Won,

Liman,

et al. 2023

Cells

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“…In this study, we generated an atlas of mouse blood CD8 + T cells to resolve the unclear relationship between unconventional antigen-inexperienced subsets: CD8 + AIMT cells ( 13 , 30 ) and two CD8 + T-cell subsets with upregulated type I interferon responsive genes ( 16 , 18 ). By comparing our and previously published data ( 16 ), we found out that naive CD8 + Ly6C + T cells have a gene expression profile largely corresponding to AIMT cells, which is consistent with the idea that they represent AIMT cell precursors ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections

Paprčková

Niederlová²,

Moudrá³

et al. 2022

Front. Immunol.

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Mature T cells are selected for recognizing self-antigens with low to intermediate affinity in the thymus. Recently, the relative differences in self-reactivity among individual T-cell clones were appreciated as important factors regulating their fate and immune response, but the role of self-reactivity in T-cell biology is incompletely understood. We addressed the role of self-reactivity in T-cell diversity by generating an atlas of mouse peripheral CD8+ T cells, which revealed two unconventional populations of antigen-inexperienced T cells. In the next step, we examined the steady-state phenotype of monoclonal T cells with various levels of self-reactivity. Highly self-reactive clones preferentially differentiate into antigen-inexperienced memory-like cells, but do not form a population expressing type I interferon-induced genes, showing that these two subsets have unrelated origins. The functional comparison of naïve monoclonal CD8+ T cells specific to the identical model antigen did not show any correlation between the level of self-reactivity and the magnitude of the immune response.

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“…A substantial proportion of Ag-inexperienced T cells in unmanipulated mice express phenotypic markers of immune memory (7,129,130). These cells have been primarily defined within the CD8 1 T cell lineage of mice.…”

Section: Conventional T Cells With Innate-like Functionsmentioning

confidence: 99%

“…Innate-like memory T cells express NKG2D and can respond to cytokine signals (e.g., IL-12 and IL-18) to induce IFN-g production and bystander killing in an Ag-independent manner. These cells contribute to clearance of bacterial and viral infections while maintaining tolerance against self-antigens (7,129,130). These cells can also infiltrate tumors where they express PD-1 (programmed death 1) and may serve as targets for checkpoint inhibitors (133).…”

Section: Conventional T Cells With Innate-like Functionsmentioning

confidence: 99%

Innate and Innate-like Effector Lymphocytes in Health and Disease

Kaer

Postoak

Song

et al. 2022

The Journal of Immunology

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Lymphocytes can be functionally partitioned into subsets belonging to the innate or adaptive arms of the immune system. Subsets of innate and innate-like lymphocytes may or may not express Ag-specific receptors of the adaptive immune system, yet they are poised to respond with innate-like speed to pathogenic insults but lack the capacity to develop classical immunological memory. These lymphocyte subsets display a number of common properties that permit them to integrate danger and stress signals dispatched by innate sensor cells to facilitate the generation of specialized effector immune responses tailored toward specific pathogens or other insults. In this review, we discuss the functions of distinct subsets of innate and innate-like lymphocytes. A better understanding of the mechanisms by which these cells are activated in different contexts, their interactions with other immune cells, and their role in health and disease may inform the development of new or improved immunotherapies.

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Signals for antigen-independent differentiation of memory CD8+ T cells

Cited by 4 publications

References 106 publications

Proinflammatory IFNγ Is Produced by but Not Required for the Generation of Eomes+ Thymic Innate CD8 T Cells

Proinflammatory IFNγ Is Produced by but Not Required for the Generation of Eomes+ Thymic Innate CD8 T Cells

Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections

Innate and Innate-like Effector Lymphocytes in Health and Disease

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