Related Experiment Video

Updated: Aug 6, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
08:20

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol

Published on: December 30, 2016

TGF-beta 1 differentially regulates IL-2 expression and [3H]-thymidine incorporation in CD3 epsilon mAb- and CD28

S C McKarns1, N E Kaminski

  • 1Department of Pharmacology and Toxicology, B330 Life Sciences Building, Michigan State University, East Lansing, MI 48824-1317, USA.

Immunopharmacology
|August 11, 2000
PubMed

Transforming growth factor-beta(1) (TGF-beta(1)) is a critical bifunctional regulator of inflammatory responses. Evidence strongly suggests that these regulatory consequences are, at least in part, a result of profound pleiotropic effects on T lymphocyte effector function. The mechanisms underlying the contradictory biological effects of TGF-beta(1) remain ambiguous. The objective of the present studies was to test the hypothesis that the concentration of TGF-beta(1) and the temporal relationship between activation of the T cell receptor (TCR) and the TGF-beta receptor regulate the effect of TGF-beta(1) on T lymphocyte activation and proliferation. Toward this end, we have quantified the concentration- and time-dependent effect of TGF-beta(1) on interleukin-2 (IL-2) protein secretion as an index of T lymphocyte activation and [3H]-thymidine incorporation as an index of cell proliferation in primary splenocytes and thymocytes. Our results suggest that TGF-beta(1) stimulates IL-2 production at low concentrations (0.1-1 pg/ml) and conversely inhibits IL-2 production at high concentrations (1-10 ng/ml) in CD3epsilon monoclonal antibody (mAb)+/-CD28 mAb-activated splenocytes. Additionally, concentrations of TGF-beta(1) that stimulate IL-2 production in CD3epsilon mAb+CD28 mAb-activated splenocytes concominantly inhibit splenocyte proliferation under similar conditions. Furthermore, we provide evidence suggesting that the effects of TGF-beta(1) on T lymphocytes are dependent upon the temporal relationship between activation of the TCR and the TGF-beta receptor. A time-dependent loss of a stimulatory effect and a concomitant gain of an inhibitory response by TGF-beta(1) on IL-2 production in response to CD3epsilon and CD28 mAbs is observed when TGF-beta(1) is added following T lymphocyte activation. In summary, these data unequivocally demonstrate that the orchestration of paradoxical effects of TGF-beta(1) on T-lymphocyte function is dependent upon the concentration of TGF-beta(1) and the temporal relationship between activation of signaling through the TCR and the TGF-beta receptor. Future mechanistic studies addressing the putative role that these factors play in modulating the effects of TGF-beta(1) on T lymphocyte activity will undoubtedly provide valuable insight towards the pharmacological intervention of inflammatory responses.

More Related Videos

Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay06:15

Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay

Published on: September 7, 2018

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice07:07

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice

Published on: June 27, 2020

Related Concept Videos

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...