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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 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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B Cell Activation and Differentiation01:24

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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.
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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Updated: Jun 10, 2025

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
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Neuropeptide signalling orchestrates T cell differentiation.

Yu Hou1,2,3, Linyu Sun1,3, Martin W LaFleur1,4

  • 1Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA, USA.

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Neurons regulate T helper 1 (TH1) cell differentiation via the neuropeptide CGRP. This neuroimmune circuit enhances anti-viral responses by promoting TH1 cell activity during infection.

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Area of Science:

  • Immunology
  • Neuroscience
  • Molecular Biology

Background:

  • The balance between T helper 1 (TH1) cells and other TH cell subsets is crucial for effective anti-viral and anti-tumour immunity.
  • The precise mechanisms governing TH1 cell differentiation remain incompletely understood.

Purpose of the Study:

  • To investigate the dynamic regulation of TH1 cell differentiation in vitro and in vivo.
  • To identify key regulators of TH1 cell fate determination.

Main Methods:

  • Utilized a dichotomous TH1-TH2 cell culture system for regulator identification.
  • Employed in vitro and in vivo CRISPR screens for systematic validation of regulatory functions.
  • Analyzed the role of Receptor Activity-Modifying Protein 3 (RAMP3) and calcitonin gene-related peptide (CGRP) signaling.

Main Results:

  • RAMP3 plays a cell-intrinsic role in TH1 cell differentiation.
  • Extracellular CGRP signaling via RAMP3-CALCRL receptor restricts TH2 and promotes TH1 differentiation through CREB and ATF3 activation.
  • ATF3 induces Stat1 expression, a critical TH1 regulator.
  • Neuronal CGRP interacts with T cell RAMP3 during viral infection, enhancing TH1 and CD8+ T cell anti-viral responses.

Conclusions:

  • Identified a neuroimmune circuit involving neuronal CGRP and T cell RAMP3 in TH1 cell fate determination.
  • Demonstrated that CGRP signaling promotes TH1 differentiation and enhances anti-viral immunity.
  • Established a novel mechanism for neuronal participation in adaptive immune responses during viral infections.