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Published on: February 28, 2019
CD70-CD27 interaction augments CD8+ T-cell activation by human epidermal Langerhans cells
Marta E Polak1, Louise Newell, Vadim Y Taraban
1Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
Insights
Human skin Langerhans cells (LCs) are superior to dermal dendritic cells (DDCs) in activating memory CD8+ T cells. This enhanced CD8+ T cell immunity by LCs is dependent on CD70 signaling, crucial for fighting skin infections and cancer.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Human skin contains epidermal Langerhans cells (LCs) and dermal dendritic cells (DDCs) with distinct immune functions.
- While their roles in CD4+ T cell and humoral immunity are known, their regulation of memory CD8+ T cell responses is less understood.
Purpose of the Study:
- To compare the capacity of human LCs and DDCs in inducing antigen-specific responses in memory CD8+ T cells.
- To investigate the mechanisms underlying differential CD8+ T cell activation by epidermal versus dermal dendritic cells.
Main Methods:
- Human LCs and DDCs were matured using tumor necrosis factor-α.
- The induction of antigen-specific cytokine production and proliferation of memory CD8+ T cells was assessed.
- Cross-presentation and direct presentation of viral antigens were evaluated.
- Expression of CD70 on LCs and DDCs was analyzed, and CD70-CD27 signaling was blocked to assess its role.
Main Results:
- Both epidermal LCs and dermal DDCs efficiently activated CD8+ T cells.
- LCs demonstrated superior constitutive capacity for cross-presentation of CD8+ epitopes and direct presentation of viral antigens compared to DDCs.
- LCs exhibited higher CD70 expression.
- Blocking CD70-CD27 signaling abrogated the superior CD8+ T cell activation by LCs, indicating CD70 dependence.
Conclusions:
- Human Langerhans cells play a pivotal role in skin CD8+ T cell immunity.
- The superior activation of CD8+ T cells by LCs is mediated by CD70-dependent signaling.
- Regulating CD70 expression on LCs is crucial for enhancing immunity against skin pathogens and cancer.
Abstract:
Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments exhibit functional differences in their induction of CD4+ T-cell and humoral immune responses; however, differences in the regulation of memory CD8+ T-cell responses by human skin DCs remain poorly characterized. We tested the capacity of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce antigen-specific cytokine production and proliferation of memory CD8+ cells. Although tumor necrosis factor-α-matured human DCs from both epidermal and dermal compartments showed efficient potential to activate CD8+ cells, LCs were constitutively more efficient than DDCs in cross-presenting CD8+ epitopes, as well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8+ T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27 signaling demonstrated that superiority of CD8+ activation by epidermal LC is CD70 dependent. This CD70-related activation of CD8+ cells by LCs denotes a central role of LCs in CD8+ immunity in skin, and suggests that regulation of LC CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer.
