scholarly journals Potential for innate-like responsiveness of resident T cells in human skin: a new perspective on tissue immune-surveillance

The Lancet ◽  
2016 ◽  
Vol 387 ◽  
pp. S108
Author(s):  
Richard Woolf ◽  
Oliver Nussbaumer ◽  
Adrian Hayday
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Immune Surveillance ◽  
New Perspective

scholarly journals Epidermis instructs skin homing receptor expression in human T cells

Blood ◽  
2012 ◽  
Vol 120 (23) ◽  
pp. 4591-4598 ◽  
Author(s):  
Michelle L. McCully ◽  
Kristin Ladell ◽  
Svetlana Hakobyan ◽  
Robert E. Mansel ◽  
David A. Price ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Human Skin ◽  
Memory T Cells ◽  
Immune Surveillance ◽  
Receptor Expression ◽  
Epidermal Keratinocytes ◽  
Specific Factor ◽  
Peripheral Tissues ◽  
Preferential Expression

Abstract The localization of memory T cells to human skin is essential for long-term immune surveillance and the maintenance of barrier integrity. Although the mechanisms controlling memory T-cell migration to peripheral tissues are poorly understood, the current paradigm includes the localized secretion of “imprinting” signals from tissue-resident dendritic cells in the draining lymph nodes. Here we show that CCR8 expression by newly activated naive T cells is regulated by skin-specific factor(s) derived primarily from epidermal keratinocytes, thereby providing a mechanism for the preferential expression of CCR8 by skin-resident memory T cells. Importantly, no such effects were observed after coculture with primary cells from skin-unrelated epithelia, including mesothelium and small intestine. The keratinocyte-derived CCR8-inducing factor(s) were soluble, and independent of vitamins A and D. Furthermore, the induction of CCR8 under these conditions correlated with an increase in cutaneous lymphocyte-associated antigen expression. Our findings challenge current tissue homing paradigms, especially those involving CCR10, and emphasize the importance of steady-state epidermis rather than tissue-resident dendritic cells in controlling the localization of memory T cells within human skin.

scholarly journals αβγδ T cells play a vital role in fetal human skin development and immunity

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
René Reitermaier ◽  
Thomas Krausgruber ◽  
Nikolaus Fortelny ◽  
Tanya Ayub ◽  
Pablo Augusto Vieyra-Garcia ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Skin ◽  
Immune Surveillance ◽  
Immune Defense ◽  
Fetal Skin ◽  
Sequencing Data ◽  
Double Positive ◽  
Ligand Interaction ◽  
Skin Development

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αβγδ T cells displayed little overlap of CDR3 sequences with single-positive αβ T cells. Gene signatures, cytokine profiles and in silico receptor–ligand interaction studies indicate their contribution to early skin development. DP αβγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

scholarly journals HIV-1 Selection by Epidermal Dendritic Cells during Transmission across Human Skin

1998 ◽  
Vol 187 (10) ◽  
pp. 1623-1631 ◽  
Author(s):  
Jeanette C. Reece ◽  
Amanda J. Handley ◽  
E. John Anstee ◽  
Wayne A. Morrison ◽  
Suzanne M. Crowe ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Human Skin ◽  
Cell Sorting ◽  
Virus Entry ◽  
Skin Explants ◽  
Skin Uptake ◽  
Virus Exposure ◽  
Epidermal Dendritic Cells ◽  
Hiv 1

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179–1181.), and this selection may occur during virus entry and carriage to the lymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epidermis were recovered from the cells emigrating from the skin explants. Dermis and epidermis were separated by dispase digestion after virus exposure to determine the site of viral selection within the skin. Uptake and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferred by emigrants from the epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+, CD4+ T cells were found in both the dermal and epidermal emigrant cells. After cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found in both the dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective infection of the immature epidermal dendritic cells represents the cellular mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor.

Regulatory T Cells Inhibit CD8+ T-Cell Tissue Invasion in Human Skin Graft-Versus-Host Reactions

2012 ◽  
Vol 94 (5) ◽  
pp. 456-464 ◽  
Author(s):  
Emily Mavin ◽  
Shaheda S. Ahmed ◽  
Graeme O’Boyle ◽  
Brie Turner ◽  
Stephen Douglass ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Human Skin ◽  
Skin Graft ◽  
Cd8 T Cell ◽  
Graft Versus Host ◽  
Tissue Invasion ◽  
Cell Tissue

scholarly journals Brucella Peptide Cross-Reactive MHC I Presentation Activates SIINFEKL-Specific TCR Expressing T Cells

2018 ◽  
Author(s):  
Jerome S. Harms ◽  
Mike Khan ◽  
Cherisse Hall ◽  
Gary A. Splitter ◽  
E. Jane Homan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Pathogenic Bacteria ◽  
Cell Activation ◽  
Immune Surveillance ◽  
Cross Reactivity ◽  
Near Neighbor ◽  
Target Cells ◽  
Mhc I

ABSTRACTBrucella spp are intracellular pathogenic bacteria remarkable in their ability to escape immune surveillance and therefore inflict a state of chronic disease within the host. To enable further immune response studies, Brucella were engineered to express the well characterized chicken ovalbumin (OVA). Surprisingly, we found that CD8 T cells bearing T cell receptors (TCR) nominally specific for the OVA peptide SIINFEKL (OT-1) reacted to parental Brucella-infected targets as well as OVA-expressing Brucella variants in cytotoxicity assays. Furthermore, splenocytes from Brucella immunized mice produced IFN-γ and exhibited cytotoxicity in response to SIINFEKL-pulsed target cells. To determine if the SIINFEKL-reactive OT-1 TCR could be cross-reacting to Brucella peptides, we searched the Brucella proteome using an algorithm to generate a list of near-neighbor nonamer peptides that would bind to H2Kb. Selecting five Brucella peptide candidates, along with controls, we verified that several of these peptides mimicked SIINFEKL resulting in T cell activation through the “SIINFEKL-specific” TCR. Activation was dependent on peptide concentration as well as sequence. Our results underscore the complexity and ubiquity of cross-reactivity in T cell recognition. This cross-reactivity may enable microbes such as Brucella to escape immune surveillance by presenting peptides similar to the host, and may also lead to the activation of autoreactive T cells.

scholarly journals Dendritic cell targeting with Fc-enhanced CD40 antibody agonists induces durable antitumor immunity in humanized mouse models of bladder cancer

2021 ◽  
Vol 13 (594) ◽  
pp. eabd1346
Author(s):  
Christopher S. Garris ◽  
Jeffrey L. Wong ◽  
Jeffrey V. Ravetch ◽  
David A. Knorr
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Mouse Models ◽  
Antitumor Immunity ◽  
Bladder Tumor ◽  
Immune Surveillance ◽  
Disease Recurrence ◽  
Bcg Therapy ◽  
Agonist Antibody

Intravesical immunotherapy using Bacille Calmette-Guérin (BCG) attenuated bacteria delivered transurethrally to the bladder has been the standard of care for patients with high-risk non–muscle-invasive bladder cancer (NMIBC) for several decades. BCG therapy continues to be limited by high rates of disease recurrence and progression, and patients with BCG-unresponsive disease have few effective salvage therapy options besides radical cystectomy, highlighting a need for new therapies. We report that the immune-stimulatory receptor CD40 is highly expressed on dendritic cells (DCs) within the bladder tumor microenvironment of orthotopic bladder cancer mouse models, recapitulating CD40 expression by DCs found in human disease. We demonstrate that local CD40 agonism in mice with orthotopic bladder cancer through intravesical delivery of anti-CD40 agonist antibodies drives potent antitumor immunity and induces pharmacodynamic effects in the bladder tumor microenvironment, including a reduction in CD8+ T cells with an exhausted phenotype. We further show that type 1 conventional DCs (cDC1) and CD8+ T cells are required for both bladder cancer immune surveillance and anti-CD40 agonist antibody responses. Using orthotopic murine models humanized for CD40 and Fcγ receptors, we demonstrate that intravesical treatment with a fully human, Fc-enhanced anti-CD40 agonist antibody (2141-V11) induces robust antitumor activity in both treatment-naïve and treatment-refractory settings, driving long-term systemic antitumor immunity with no evidence of systemic toxicity. These findings support targeting CD40-expressing DCs in the bladder cancer microenvironment through an intravesical agonistic antibody approach for the treatment of NMIBC.

scholarly journals IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization

2016 ◽  
Vol 213 (10) ◽  
pp. 2147-2166 ◽  
Author(s):  
Juhan Yoon ◽  
Juan Manuel Leyva-Castillo ◽  
Guoxing Wang ◽  
Claire Galand ◽  
Michiko K. Oyoshi ◽  
...  
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Cd4 T Cells ◽  
Mouse Skin ◽  
Skin Inflammation ◽  
Serum Levels ◽  
Skin Lesions ◽  
Tape Stripping ◽  
Keratinocyte Proliferation ◽  
Th22 Cells

Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC-derived IL-23 is known to act on CD4+ T cells to induce IL-22 production. However, the mechanisms that drive IL-23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up-regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4+ T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD.

Isolation of T cells from mouse and human skin

1996 ◽  
pp. 1489-1501
Author(s):  
A ELBE ◽  
C AFOSTER ◽  
G STINGL
Keyword(s):  
T Cells ◽  
Human Skin
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