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Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

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

ORGANISM(S): Mus musculus

PROVIDER: GSE147908 | GEO | 2020/04/02

REPOSITORIES: GEO

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Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses.

Project description:CD8+ tissue-resident memory T cells (TRM cells) are poised at the portals of infection and provide long-term protective immunity. Despite their critical roles, the precise mechanics governing TRM cell reactivation in situ are unknown. Using a TCR-transgenic Nur77-GFP reporter to distinguish "antigen-specific" from "bystander" reactivation, we demonstrate that lung CD8+ TRM cells are reactivated more quickly, yet less efficiently, than their counterparts in the draining LNs (TLN cells). Global profiling of reactivated memory T cells revealed tissue-defined and temporally regulated recall response programs. Unlike the reactivation of CD8+ TLN cells, which is strictly dependent on CD11c+XCR1+ APCs, numerous antigen-presenting partners, both hematopoietic and non-hematopoietic, were sufficient to reactivate lung CD8+ TRM cells, but the quality of TRM cell functional responses depended on the identity of the APCs. Together, this work uncovers fundamental differences in the activation kinetics, mechanics, and effector responses between CD8+ memory T cells in peripheral vs. lymphoid organs, revealing a novel tissue-specific paradigm for the reactivation of memory CD8+ T cells.

| S-EPMC7398161 | biostudies-literature

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [II]

Project description:Temporal transcriptome profiling of TCR-reactivated (P14) and bystander-reactivated (OT-I) memory T cells in the lung and mediastinal lymph node based on Nur77-GFP reporter expression and CD98 expression

2020-04-02 | GSE147907 | GEO

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [I]

Project description:Global profiling to investigate the consequence of the lack of TAP-1 on hematopoetic cell or non-hematopoetic cell on the qualitative response of reactivated antigen-specific Trm cells

2020-04-02 | GSE147906 | GEO

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

Project description:Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

| PRJNA622522 | ENA

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [II]

Project description:Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [II]

| PRJNA622525 | ENA

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [I]

Project description:Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [I]

| PRJNA622526 | ENA

Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses.

Project description:Skin-resident dendritic cells (DCs) are well positioned to encounter cutaneous pathogens and are required for the initiation of adaptive immune responses. There are at least three subsets of skin DC- Langerhans cells (LC), Langerin(+) dermal DCs (dDCs), and classic dDCs. Whether these subsets have distinct or redundant function in vivo is poorly understood. Using a Candida albicans skin infection model, we have shown that direct presentation of antigen by LC is necessary and sufficient for the generation of antigen-specific T helper-17 (Th17) cells but not for the generation of cytotoxic lymphocytes (CTLs). In contrast, Langerin(+) dDCs are required for the generation of antigen specific CTL and Th1 cells. Langerin(+) dDCs also inhibited the ability of LCs and classic DCs to promote Th17 cell responses. This work demonstrates that skin-resident DC subsets promote distinct and opposing antigen-specific responses.

| S-EPMC3163010 | biostudies-literature

Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells.

Project description:T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity.

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RD antigen based nanovaccine imparts long term protection by inducing memory response against experimental murine tuberculosis.

Project description:BackgroundThe absence of certain genomic loci that are present in most of the virulent strains of Mycobacterium tuberculosis as well as lack of lasting memory responses are some of the major causes attributed to the non effectiveness of Bacille Calmette-Gue'rin (BCG) vaccine. Immunization schedules addressing these issues can offer better strategy for protection against tuberculosis.MethodsThe immunological responses evoked upon administration of archaeosome based antigen delivery system comprising T cell antigen, Rv3619c (an ESAT-6 family protein), has been assessed against experimental murine tuberculosis in BALB/c mice.ResultsArchaeosome based subunit vaccine has been found to elicit type-1 cytokines in the immunized mice. Besides effective T cell memory response, the Rv3619c based vaccine was able to reduce mycobacterial burden in the animals challenged with Mycobacterium tuberculosis infection.ConclusionThe data of the present study suggest that archaeosome encapsulated RD gene products offer substantial protection against M. tuberculosis infection.

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Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs.

Project description:ILCs and T helper cells have been shown to exert bi-directional regulation in mice. However, how crosstalk between ILCs and CD4+ T cells influences immune function in humans is unknown. Here we show that human intestinal ILCs co-localize with T cells in healthy and colorectal cancer tissue and display elevated HLA-DR expression in tumor and tumor-adjacent areas. Although mostly lacking co-stimulatory molecules ex vivo, intestinal and peripheral blood (PB) ILCs acquire antigen-presenting characteristics triggered by inflammasome-associated cytokines IL-1β and IL-18. IL-1β drives the expression of HLA-DR and co-stimulatory molecules on PB ILCs in an NF-κB-dependent manner, priming them as efficient inducers of cytomegalovirus-specific memory CD4+ T-cell responses. This effect is strongly inhibited by the anti-inflammatory cytokine TGF-β. Our results suggest that circulating and tissue-resident ILCs have the intrinsic capacity to respond to the immediate cytokine milieu and regulate local CD4+ T-cell responses, with potential implications for anti-tumor immunity and inflammation.

| S-EPMC7184749 | biostudies-literature

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