Antigen reactivity defines tissue-resident memory and exhausted T cells in tumours.

CD8 T cells are a key weapon in the therapeutic armamentarium against cancer. While CD8 CD103 T cells with a tissue-resident memory T (T ) cell phenotype have been favourably correlated with patient prognoses , the tumour microenvironment also contains dysfunctional exhausted T (T ) cells that exhibit a myriad of T -like features, leading to conflation of these two populations. Here, we deconvolute T and T cells within the intratumoural CD8 CD103 T cell pool across human cancers, ascribing markers and gene signatures that distinguish these CD8 populations and enable their functional distinction.

Unique properties of tissue-resident memory T cells in the lungs: implications for COVID-19 and other respiratory diseases.

Tissue-resident memory T (T) cells were originally identified as a tissue-sequestered population of memory T cells that show lifelong persistence in non-lymphoid organs. That definition has slowly evolved with the documentation of T cells having variable terms of tissue residency combined with a capacity to return to the wider circulation. Nonetheless, reductionist experiments have identified an archetypical population of T cells showing intrinsic permanent residency in a wide range of non-lymphoid organs, with one notable exception: the lungs.

Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity.

Tissue-resident memory T (T) cells are non-recirculating cells that exist throughout the body. Although T cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze T cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate T cell function, durability and malleability.

Should I stay or should I go-Reconciling clashing perspectives on CD4 tissue-resident memory T cells.

Two recent studies on CD4 T cells in nonlymphoid tissues reveal a combination of memory cell retention and emigration.

Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses.

Although tissue-resident memory T cells (T cells) are critical in fighting infection, their fate after local pathogen re-encounter is unknown. Here we found that skin T cells engaged virus-infected cells, proliferated in situ in response to local antigen encounter and did not migrate out of the epidermis, where they exclusively reside. As a consequence, secondary T cells formed from pre-existing T cells, as well as from precursors recruited from the circulation.

Staged development of long-lived T-cell receptor αβ T17 resident memory T-cell population to Candida albicans after skin infection.

Background: Candida albicans is a dimorphic fungus to which human subjects are exposed early in life, and by adulthood, it is part of the mycobiome of skin and other tissues. Neonatal skin lacks resident memory T (T) cells, but in adults the C albicans skin test is a surrogate for immunocompetence. Young adult mice raised under specific pathogen-free conditions are naive to C albicans and have been shown recently to have an immune system resembling that of neonatal human subjects.

Development of a Novel CD4 TCR Transgenic Line That Reveals a Dominant Role for CD8 Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria.

We describe an MHC class II (I-A)-restricted TCR transgenic mouse line that produces CD4 T cells specific for species. This line, termed PbT-II, was derived from a CD4 T cell hybridoma generated to blood-stage ANKA (PbA). PbT-II cells responded to all species and stages tested so far, including rodent (PbA, NK65, AS, and 17XNL) and human () blood-stage parasites as well as irradiated PbA sporozoites.

Sustained accumulation of antigen-presenting cells after infection promotes local T-cell immunity.

Antigen-presenting cells (APC), such as dendritic cells (DC) and macrophages, are critical for T-cell-mediated immunity. Although it is established that memory T cells accumulate and persist in peripheral tissues after the resolution of infection, whether this is also the case for APC remains unclear. Here, we report that CCR2-dependent cells infiltrate skin during acute infection with herpes simplex virus (HSV)-1 and subsequently give rise to localized populations of DCs and macrophages.

Cutting Edge: Tissue-Resident Memory T Cells Generated by Multiple Immunizations or Localized Deposition Provide Enhanced Immunity.

Tissue-resident memory T cells (T) have been shown to afford superior protection against infection, particularly against pathogens that enter via the epithelial surfaces of the body. Although T are often concentrated at sites of prior infection, it has been shown that T can disseminate throughout the body. We examined the relative effectiveness of global versus targeted CD8 T lodgment in skin.

Liver-Resident Memory CD8 T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection.

In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8 T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids.

Skin CD4(+) memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation.

Although memory T cells within barrier tissues can persist as permanent residents, at least some exchange with blood. The extent to which this occurs is unclear. Here we show that memory CD4(+) T cells in mouse skin are in equilibrium with the circulation at steady state.

Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes.

Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice.

The frequency of mucosal-associated invariant T cells is selectively increased in dermatitis herpetiformis.

Background/objectives: Mucosal-associated invariant T (MAIT) cells are a novel subset of innate-like T-cells that are enriched in mucosal tissues. Their presence in human skin has only recently been recognised. We describe the expression of skin-tropic molecules on human skin MAIT cells at steady state and investigate their contribution to various dermatoses with known T-cell involvement.

Transcriptional Analysis of T Cells Resident in Human Skin.

Human skin contains various populations of memory T cells in permanent residence and in transit. Arguably, the best characterized of the skin subsets are the CD8(+) permanently resident memory T cells (TRM) expressing the integrin subunit, CD103. In order to investigate the remaining skin T cells, we isolated skin-tropic (CLA(+)) helper T cells, regulatory T cells, and CD8(+) CD103(-) T cells from skin and blood for RNA microarray analysis to compare the transcriptional profiles of these groups.

T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate.

Tissue-resident memory T (Trm) cells contribute to local immune protection in non-lymphoid tissues such as skin and mucosa, but little is known about their transcriptional regulation. Here we showed that CD8(+)CD103(+) Trm cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. We demonstrated that the T-box transcription factors (TFs) Eomes and T-bet combined to control CD8(+)CD103(+) Trm cell formation, such that their coordinate downregulation was crucial for TGF-β cytokine signaling.

Tissue-Resident Memory T Cells and Fixed Immune Surveillance in Nonlymphoid Organs.

T cell immunity is often defined in terms of memory lymphocytes that use the blood to access a range of organs. T cells are involved in two patterns of recirculation. In one, the cells shuttle back and forth between blood and secondary lymphoid organs, whereas in the second, memory cells recirculate between blood and nonlymphoid tissues.