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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells

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IL-10-Engineered Dendritic Cells Modulate Allogeneic CD8+ T Cell Responses.

Marta Fortunato1,2, Giada Amodio1, Silvia Gregori1

  • 1Mechanisms of Peripheral Tolerance Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

International Journal of Molecular Sciences
|June 10, 2023
PubMed
Summary

Genetically engineered human tolerogenic dendritic cells (tolDC) overexpressing IL-10 effectively suppress cytotoxic CD8+ T cell responses. These IL-10-engineered tolDC show promise for inducing tolerance in transplantation and T-cell mediated diseases.

Keywords:
CD8+ T cellsIL-10allogeneic responsesdendritic cells

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Area of Science:

  • Immunology
  • Cell Therapy
  • Transplantation Immunology

Background:

  • Tolerogenic dendritic cells (tolDC) are crucial for immune homeostasis and tolerance induction.
  • Existing cell-based therapies aim to leverage tolDC for T-cell mediated diseases and transplantation.
  • Genetically engineered tolDC offer enhanced therapeutic potential.

Purpose of the Study:

  • To investigate the capacity of IL-10-overexpressing human tolDC (DCIL-10) to modulate cytotoxic CD8+ T cell responses.
  • To assess the stability and efficacy of DCIL-10 in a pro-inflammatory environment.
  • To evaluate DCIL-10 as a cellular product for inducing transplantation tolerance.

Main Methods:

  • Development of a lentiviral vector protocol for genetically engineered human tolDC overexpressing IL-10 (DCIL-10).
  • Assessment of DCIL-10's ability to promote allo-specific T regulatory type 1 (Tr1) cells.
  • Evaluation of DCIL-10's modulation of allogeneic CD4+ and CD8+ T cell responses in vitro and in vivo.
  • Analysis of CD8+ T cell proliferation, activation, anergy, and cytotoxic activity following DCIL-10 stimulation.

Main Results:

  • DCIL-10 successfully promote allo-specific Tr1 cells and modulate allogeneic CD4+ T cell responses.
  • DCIL-10 significantly reduce allogeneic CD8+ T cell proliferation and activation in mixed lymphocyte reactions (MLR).
  • Long-term DCIL-10 stimulation induces allo-specific anergic CD8+ T cells without exhaustion, displaying limited cytotoxic activity.

Conclusions:

  • Stable IL-10 overexpression in human dendritic cells generates a potent population of tolDC.
  • DCIL-10 effectively modulate cytotoxic allogeneic CD8+ T cell responses, inducing anergy rather than exhaustion.
  • DCIL-10 represent a promising cellular therapy for inducing tolerance in allogeneic transplantation and T-cell mediated diseases.