Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection

Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8+ memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-γ–dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity.

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Renewal of Peripheral CD8+Memory T Cells During Secondary Viral Infection of Antibody-Sufficient Mice

The Journal of Immunology ◽

10.4049/jimmunol.170.11.5597 ◽

2003 ◽

Vol 170 (11) ◽

pp. 5597-5606 ◽

Cited By ~ 11

Author(s):

Linda S. Cauley ◽

Tres Cookenham ◽

Robert J. Hogan ◽

Sherry R. Crowe ◽

David L. Woodland

Keyword(s):

T Cells ◽

Viral Infection ◽

Memory T Cells ◽

Cd8 Memory T Cells

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Interplay of Inflammatory, Antigen and Tissue-Derived Signals in the Development of Resident CD8 Memory T Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.636240 ◽

2021 ◽

Vol 12 ◽

Author(s):

Curtis J. Pritzl ◽

Mark A. Daniels ◽

Emma Teixeiro

Keyword(s):

T Cells ◽

Inflammatory Cytokines ◽

Memory T Cells ◽

First Line ◽

Resident Memory T Cells ◽

Cd8 Memory T Cells ◽

Initial Research ◽

Pro Inflammatory Cytokines ◽

Inflammatory Tissue

CD8 positive, tissue resident memory T cells (TRM) are a specialized subset of CD8 memory T cells that surveil tissues and provide critical first-line protection against tumors and pathogen re-infection. Recently, much effort has been dedicated to understanding the function, phenotype and development of TRM. A myriad of signals is involved in the development and maintenance of resident memory T cells in tissue. Much of the initial research focused on the roles tissue-derived signals play in the development of TRM, including TGFß and IL-33 which are critical for the upregulation of CD69 and CD103. However, more recent data suggest further roles for antigenic and pro-inflammatory cytokines. This review will focus on the interplay of pro-inflammatory, tissue and antigenic signals in the establishment of resident memory T cells.

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Immune Trait Shifts in Association With Tobacco Smoking: A Study in Healthy Women

Frontiers in Immunology ◽

10.3389/fimmu.2021.637974 ◽

2021 ◽

Vol 12 ◽

Author(s):

Giulia Piaggeschi ◽

Simona Rolla ◽

Niccolò Rossi ◽

Davide Brusa ◽

Alessio Naccarati ◽

...

Keyword(s):

T Cells ◽

Tobacco Smoking ◽

Immune Cell ◽

Memory T Cells ◽

Smoking Status ◽

Cell Subset ◽

Activation Marker ◽

Healthy Women ◽

Immune Traits ◽

Cd8 Memory T Cells

Tobacco smoking is known to impact circulating levels of major immune cells populations, but its effect on specific immune cell subsets remains poorly understood. Here, using high-resolution data from 223 healthy women (25 current and 198 never smokers), we investigated the association between smoking status and 35,651 immune traits capturing immune cell subset frequencies. Our results confirmed that active tobacco smoking is associated with increased frequencies of circulating CD8+ T cells expressing the CD25 activation marker. Moreover, we identified novel associations between smoking status and relative abundances of CD8+ CD25+ memory T cells, CD8+ memory T cells expressing the CCR4 chemokine receptor, and CD4+CD8+ (double-positive) CD25+ T cells. We also observed, in current smokers, a decrease in the relative frequencies of CD4+ T cells expressing the CD38 activation marker and an increase in class-switched memory B cell isotypes IgA, IgG, and IgE. Finally, using data from 135 former female smokers, we showed that the relative frequencies of immune traits associated with active smoking are usually completely restored after smoking cessation, with the exception of subsets of CD8+ and CD8+ memory T cells, which persist partially altered. Our results are consistent with previous findings and provide further evidence on how tobacco smoking shapes leukocyte cell subsets proportion toward chronic inflammation.

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C-Myc regulation by costimulatory signals modulates the generation of CD8 + memory T cells during viral infection

Open Biology ◽

10.1098/rsob.150208 ◽

2016 ◽

Vol 6 (1) ◽

pp. 150208 ◽

Cited By ~ 11

Author(s):

Mohammad Haque ◽

Jianyong Song ◽

Kristin Fino ◽

Youfei Wang ◽

Praneet Sandhu ◽

...

Keyword(s):

T Cells ◽

Viral Infection ◽

Memory T Cells ◽

T Cell Memory ◽

Over Expression ◽

Specific Memory ◽

Intracellular Target ◽

Costimulatory Signals ◽

Factor C ◽

Cd8 Memory T Cells

The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8 + T cells is controlled by costimulatory molecules, which modulates the development of memory CD8 + T cells. C-Myc expression was dramatically reduced in Cd28 −/− or Ox40 −/− memory CD8 + T cells, and c-Myc over-expression substantially reversed the defects in the development of T-cell memory following viral infection. C-Myc regulated the expression of survivin, an inhibitor of apoptosis, which promoted the generation of virus-specific memory CD8 + T cells. Moreover, over-expression of survivin with bcl-xL, a downstream molecule of NF- κ B and intracellular target of costimulation that controls survival, in Cd28 −/− or Ox40 −/− CD8 + T cells, reversed the defects in the generation of memory T cells in response to viral infection. These results identify c-Myc as a key controller of memory CD8 + T cells from costimulatory signals.

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CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses

Journal of Experimental Medicine ◽

10.1084/jem.20181365 ◽

2019 ◽

Vol 216 (5) ◽

pp. 1214-1229 ◽

Cited By ~ 46

Author(s):

Lalit K. Beura ◽

Nancy J. Fares-Frederickson ◽

Elizabeth M. Steinert ◽

Milcah C. Scott ◽

Emily A. Thompson ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Cd4 T Cells ◽

Cell Activation ◽

Immune Cell ◽

Memory T Cells ◽

Cell Immunity ◽

And Migration ◽

Resident Memory T Cells ◽

Memory Cd4 T Cells

This study examines the extent to which memory CD4+ T cells share immunosurveillance strategies with CD8+ resident memory T cells (TRM). After acute viral infection, memory CD4+ T cells predominantly used residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8+ T cells. In contrast, memory CD4+ T cells were more likely to be resident within lymphoid organs than CD8+ T cells. Migration properties of memory-phenotype CD4+ T cells in non-SPF parabionts were similar, generalizing these results to diverse infections and conditions. CD4+ and CD8+ TRM shared overlapping transcriptional signatures and location-specific features, such as granzyme B expression in the small intestine, revealing tissue-specific and migration property–specific, in addition to lineage-specific, differentiation programs. Functionally, mucosal CD4+ TRM reactivation locally triggered both chemokine expression and broad immune cell activation. Thus, residence provides a dominant mechanism for regionalizing CD4+ T cell immunity, and location enforces shared transcriptional, phenotypic, and functional properties with CD8+ T cells.

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Human Tissue-Resident Memory T Cells in the Maternal–Fetal Interface. Lost Soldiers or Special Forces?

Cells ◽

10.3390/cells9122699 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2699

Author(s):

Caitlin S. DeJong ◽

Nicholas J. Maurice ◽

Stephen A. McCartney ◽

Martin Prlic

Keyword(s):

T Cells ◽

Immune System ◽

Cell Function ◽

Immune Cell ◽

Memory T Cells ◽

Critical Role ◽

Immune Cell Function ◽

Histocompatibility Complex ◽

Resident Memory T Cells ◽

Maternal Fetal Interface

The immune system plays a critical role during pregnancy, but the specific mechanisms and immune cell function needed to support pregnancy remain incompletely understood. Despite decades of research efforts, it is still unclear how the immune system maintains tolerance of fetal-derived tissues, which include most cells of the placenta and of course the fetus itself, without forfeiting the ability to protect against harmful infections. T cells recognize antigen in the context of major histocompatibility complex (MHC) encoded proteins, but classical MHC class I and II expression are diminished in fetal-derived cells. Can T cells present at the maternal–fetal interface (MFI) protect these cells from infection? Here we review what is known in regard to tissue-resident memory T (Trm) cells at the MFI. We mainly focus on how Trm cells can contribute to protection in the context of the unique features of the MFI, such as limited MHC expression as well as the temporary nature of the MFI, that are not found in other tissues.

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