Related Experiment Video

Updated: Aug 8, 2026

A Three-dimensional Thymic Culture System to Generate Murine Induced Pluripotent Stem Cell-derived Tumor Antigen-specific Thymic Emigrants
10:44

A Three-dimensional Thymic Culture System to Generate Murine Induced Pluripotent Stem Cell-derived Tumor Antigen-specific Thymic Emigrants

Published on: August 9, 2019

Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth

M D Mossalayi1, F Mentz, F Ouaaz

  • 1Molecular Immuno-Hematology Group, Pitié-Salpêtrière Hospital, Paris, France.

Blood
|June 15, 1995
PubMed

Insights

Transforming growth factor beta (TGF-β) from early thymocytes inhibits their proliferation, with CD8+ cells activating this suppressive mechanism. This suggests TGF-β regulates human T-cell output from the thymus.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Early thymocytes, crucial for adaptive immunity, undergo significant proliferation within the thymus.
  • The precise cellular interactions and cytokines governing this intrathymic proliferation remain incompletely understood.

Purpose of the Study:

  • To investigate the effects of growth factors and cellular interactions on the in vitro proliferation of early human triple-negative (TN) thymocytes.
  • To elucidate the role of transforming growth factor beta (TGF-β) in regulating early thymocyte proliferation and thymic T-cell output.

Main Methods:

  • Assayed proliferation of isolated CD2+CD3/TCR-CD4-CD8- (TN) human thymocytes.
  • Incubated TN cells with monoclonal antibodies (MoAb), interleukins (IL-2, IL-7, IL-4), and/or transforming growth factor beta (TGF-β).
  • Investigated the inhibitory effect of CD8+ cells using neutralizing anti-TGF-β MoAb and analyzed TGF-β production in cell supernatants and via fixation studies.

Main Results:

  • TN cells showed significant proliferative responses to IL-4, IL-7, or CD2-MoAb + IL-2.
  • Recombinant TGF-β or autologous CD8+ cells markedly reduced IL-2 and IL-7-induced proliferation, with IL-4-induced proliferation being less sensitive.
  • Neutralizing anti-TGF-β MoAb abolished CD8+ cell-mediated inhibition, identifying TGF-β as the key inhibitory mediator.
  • TN cells, not CD8+ cells, were the primary source of TGF-β1, which was secreted in a latent form activated upon interaction with CD8+ cells.

Conclusions:

  • TGF-β1 acts as an externally controlled, autocrine inhibitory factor for human early thymocytes.
  • Interaction between TN cells and CD8+ cells activates latent TGF-β1, regulating thymocyte proliferation.
  • This mechanism suggests a critical role for TGF-β1 in controlling thymic T-cell output.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Formation of Human Thymus Organoids in Three-Dimensional Fibrin Hydrogels03:31

Formation of Human Thymus Organoids in Three-Dimensional Fibrin Hydrogels

Published on: October 4, 2024

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Abnormal Proliferation02:23

Abnormal Proliferation

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 daughter...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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 are of three kinds RI, RII, and RIII. The RI...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
T Cell Types and Functions01:24

T Cell Types and Functions

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...