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Related Concept Videos

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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Multipotency of Hematopoietic Stem Cells01:19

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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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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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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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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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Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
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Related Experiment Video

Updated: Jan 6, 2026

In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
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Inhibitory PD-1 axis maintains high-avidity stem-like CD8+ T cells.

Jyh Liang Hor1, Edward C Schrom2, Abigail Wong-Rolle2,3

  • 1Lymphocyte Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. jyhliang.hor@nih.gov.

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Checkpoint immunotherapy relies on stem-like cytotoxic T cells. Prolonged antigen engagement, not persistent T cell receptor signaling, sustains these cells, with PD-1 fine-tuning their high-affinity expansion.

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Related Experiment Videos

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Area of Science:

  • Immunology
  • Cancer Biology
  • T cell biology

Background:

  • Stem-like cytotoxic T cells are crucial for effective cancer immunotherapy.
  • Tumor-draining lymph nodes are vital for generating and maintaining these stem-like cells.
  • Understanding factors that promote T cell stemness is key for improving immunotherapy.

Purpose of the Study:

  • To identify antigen-presentation niches in tumor-draining lymph nodes that support stem-like CD8+ T cells.
  • To elucidate the role of T cell receptor (TCR) signaling and PD-1 in maintaining T cell stemness.
  • To investigate the impact of PD-1 blockade on high-affinity T cell clones.

Main Methods:

  • Advanced three-dimensional multiplex immunofluorescence imaging.
  • In vivo studies of T cell proliferation and differentiation.
  • Analysis of T cell receptor (TCR) signaling dynamics and PD-1 pathway function.

Main Results:

  • Identified specific niches in tumor-draining lymph nodes supporting stem-like T cell expansion and affinity evolution.
  • Demonstrated that prolonged antigen engagement, not just initial priming, sustains stem-like T cell self-renewal.
  • Showed the PD-1 pathway fine-tunes TCR signaling, enabling selective expansion of high-affinity clones.

Conclusions:

  • Prolonged antigen engagement and PD-1 signaling are critical for maintaining a renewable pool of high-affinity anti-tumor T cells.
  • PD-1 blockade may disrupt this process, leading to the loss of crucial stem-like precursors.
  • Findings challenge current understanding of T cell differentiation and have implications for optimizing anti-PD-1 cancer immunotherapy strategies.