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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.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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Cell-mediated Immune Responses01:40

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Overview
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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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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Cytotoxic T Cells-mediated Immune Response01:27

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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Regulation of Hematopoietic Stem Cells01:01

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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Related Experiment Video

Updated: Mar 2, 2026

Bone Marrow Transplantation Platform to Investigate the Role of Dendritic Cells in Graft-versus-Host Disease
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Ceramide synthesis regulates T cell activity and GVHD development.

M Hanief Sofi1, Jessica Heinrichs1, Mohammed Dany2

  • 1Department of Microbiology and Immunology and.

JCI Insight
|May 19, 2017
PubMed
Summary

Targeting ceramide synthase 6 (CerS6) can reduce graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). This approach limits T-cell activation while preserving anti-leukemia effects, enhancing immunotherapy efficacy.

Keywords:
ImmunologyTransplantation

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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity

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Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Allogeneic hematopoietic cell transplantation (allo-HCT) is a vital immunotherapy for hematologic malignancies.
  • Graft-versus-host disease (GVHD) limits allo-HCT efficacy by activating donor T cells.
  • The role of ceramides, particularly ceramide synthase 6 (CerS6), in allo-HCT and GVHD is not well understood.

Purpose of the Study:

  • To investigate the role of ceramide synthase 6 (CerS6) in T-cell responses during allo-HCT.
  • To determine if CerS6 inhibition can mitigate GVHD without compromising anti-leukemia activity.

Main Methods:

  • Utilized genetic and pharmacologic methods to study CerS6 function in mouse and human T cells.
  • Assessed T-cell activation, proliferation, cytokine production, and T-cell receptor (TCR) signaling.
  • Evaluated the impact of CerS6 targeting on GVHD induction and anti-leukemia effects in vivo.

Main Results:

  • CerS6 is crucial for T-cell activation, proliferation, and cytokine production against alloantigens.
  • CerS6 deficiency or inhibition impairs T-cell receptor signaling and C16-ceramide generation.
  • Targeting CerS6 effectively reduced GVHD in mouse models and T-cell activation in vitro.
  • CerS6 was partially dispensable for the T-cell mediated anti-leukemia effect.

Conclusions:

  • CerS6 plays a critical role in allo-HCT-induced GVHD by promoting alloreactive T-cell responses.
  • Inhibiting CerS6 presents a promising strategy to control GVHD, thereby improving allo-HCT efficacy.
  • Targeting CerS6 could enhance the clinical application of allo-HCT for hematologic malignancies.