The effect of TGF-beta1 on immune responses of naïve versus memory CD4+ Th1/Th2 T cells

Eur J Immunol. 2000 Jul;30(7):2101-11. doi: 10.1002/1521-4141(200007)30:7<2101::AID-IMMU2101>3.0.CO;2-P.


The role of TGF-beta1 in the regulation of T cell responses has been perplexing, possibly because it is dependent on the type of T cell being regulated and its cytokine microenvironment. In the present study, we demonstrate that TGF-beta1 has a profound inhibitory effect on naive CD4+ T cell undergoing differentiation under defined neutral, Th1 and Th2 priming conditions. In addition, we show that if CD4+ T cells are primed in the presence of TGF-beta1, they exhibit reduced secondary anti-CD3/anti-CD28-induced and antigen-specific immune responses (even when TGF-beta is absent during the secondary response), which is not due to reduced expression of co-stimulatory molecules or to inadequate IL-2 production. Finally, with respect to the effect of TGF-beta on fully differentiated antigen-specific memory CD4+ T cells, we demonstrate that while antigen-specific activation and cytokine secretion by memory Th1 T cells is inhibited by TGF-beta1, such inhibition is associated with partial down-regulation of IL-12 receptor beta2 chain expression. In contrast, memory Th2 T cells are not subject to TGF-beta1 -mediated suppression. In summary, these studies reveal that TGF-beta1 is a powerful negative regulator of the primary immune response of CD4+ T cells, but only Th1 T cells are subject to such regulation after the memory stage of T cell differentiation has been reached. Thus, these studies define the potential regulatory role of TGF-beta1 in Th1 and Th2 T cell-mediated autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Immunologic Memory / immunology*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / immunology
  • Interleukin-4 / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • Phosphorylation
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT6 Transcription Factor
  • Th1 Cells / cytology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / immunology*


  • DNA-Binding Proteins
  • Il12rb1 protein, mouse
  • Il12rb2 protein, mouse
  • Interleukin-2
  • OVA 323-339
  • Peptide Fragments
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT6 Transcription Factor
  • Stat4 protein, mouse
  • Stat6 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin