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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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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.
Naive T cells that have not yet encountered an antigen express two primary CD...
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T Cell Types and Functions01:24

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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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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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Multipotency and Niche of Bulge Stem Cell01:06

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A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
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Cells of the Adaptive Immune Response01:23

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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Defining the niche for stem-like CD8+ T cell formation and function.

Benjamin J Broomfield1, Joanna R Groom1

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Stem-like TCF-1 positive CD8 positive T cells are crucial for long-term immunity and better disease outcomes. Their specialized microenvironments can be targeted to improve cancer immunotherapy and vaccines.

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Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • TCF-1 positive CD8 positive T cells are key for long-lived immunological memory and stem-like properties.
  • These cells contribute to sustained killing of infected cells and maintaining immune-cancer balance.
  • CD8 positive T cell differentiation is influenced by antigen, inflammation, and priming dynamics, with similar stem-like states forming in acute and chronic diseases.

Purpose of the Study:

  • To characterize the microenvironments that generate or reactivate stem-like TCF-1 positive CD8 positive T cell populations.
  • To explore the potential of targeting these stem-like T cell niches for therapeutic benefit.
  • To investigate the use of stem-like CD8 positive T cells as biomarkers for treatment efficacy.

Main Methods:

  • Characterization of specialized microenvironments in lymph nodes and tumor microenvironments.
  • Analysis of factors influencing CD8 positive T cell differentiation.
  • Investigation of stem-like TCF-1 positive CD8 positive T cell populations in different disease settings.

Main Results:

  • Identification of specific microenvironmental niches that support stem-like TCF-1 positive CD8 positive T cell generation and reactivation.
  • Demonstration that phenotypically similar stem-like TCF-1 positive CD8 positive T cell states are formed in both acute and chronic disease settings.
  • Highlighting the potential therapeutic targeting of these stem-like T cell niches.

Conclusions:

  • Targeting the stem-like CD8 positive T cell niche offers a promising strategy for enhancing vaccination and cancer immunotherapy.
  • Stem-like CD8 positive T cells can serve as valuable biomarkers to track therapeutic efficacy.
  • Understanding these specialized microenvironments is crucial for developing novel immunotherapies.