TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice.

Abstract

In previous studies, we have shown that murine CD4+CD25+ regulatory T cells produce high levels of TGF-beta1 in a cell surface and/or secreted form, and blockade of such TGF-beta1 by anti-TGF-beta curtails the ability of these cells to suppress CD25- T cell proliferation and B cell Ig production in in vitro suppressor assays. In further support for the role of TGF-beta1 in suppression by CD4+CD25+ T cells, we show in this study that another TGF-beta1-blocking molecule, recombinant latency-associated peptide of TGF-beta1 (rLAP), also reverses suppression by mouse CD4+CD25+ T cells as well as their human counterparts, CD4+CD25(high) T cells. In addition, we show that CD25- T cells exposed to CD4+CD25+ T cells in vitro manifest activation of Smad-2 and induction of CD103, the latter a TGF-beta-inducible surface integrin. In further studies, we show that while CD4+CD25+ T cells from TGF-beta1-deficient mice can suppress CD25- T cell proliferation in vitro, these cells do not protect recipient mice from colitis in the SCID transfer model in vivo, and, in addition, CD4+LAP+, but not CD4+LAP- T cells from normal mice protect recipient mice from colitis in this model. Together, these studies demonstrate that TGF-beta1 produced by CD4+CD25+ T cells is involved in the suppressor activity of these cells, particularly in their ability to regulate intestinal inflammation.

• Authors: Kazuhiko Nakamura, Atsushi Kitani, Ivan Fuss, Aasta Pedersen, Naohiko Harada, Hajime Nawata, Warren Strober
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 2 Pg. 834-42 (Jan 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 14707053 (Publication Type: Journal Article)

Chemical References

• Inflammation Mediators
• Peptide Fragments
• Protein Precursors
• Receptors, Interleukin-2
• Receptors, Transforming Growth Factor beta
• Recombinant Proteins
• TGFB1 protein, human
• Tgfb1 protein, mouse
• Transforming Growth Factor beta
• Transforming Growth Factor beta1

Topics

• Adoptive Transfer
• Animals
• CD4-Positive T-Lymphocytes (immunology, metabolism, transplantation)
• Cell Membrane (metabolism)
• Cells, Cultured
• Colitis (genetics, immunology)
• Down-Regulation (immunology)
• Female
• Humans
• Inflammation Mediators (metabolism, physiology)
• Intestinal Mucosa (immunology, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, SCID
• Peptide Fragments (biosynthesis, pharmacology)
• Protein Binding (immunology)
• Protein Precursors (biosynthesis, pharmacology)
• Receptors, Interleukin-2 (biosynthesis)
• Receptors, Transforming Growth Factor beta (physiology)
• Recombinant Proteins (pharmacology)
• Signal Transduction (immunology)
• T-Lymphocyte Subsets (immunology, metabolism, transplantation)
• T-Lymphocytes, Regulatory (immunology)
• Transforming Growth Factor beta (biosynthesis, deficiency, genetics, physiology)
• Transforming Growth Factor beta1