|
|
Blood, 1 January 2005, Vol. 105, No. 1, pp. 274-281.
Prepublished online as a Blood First Edition Paper on September 7, 2004; DOI 10.1182/blood-2003-12-4343.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Modulation of cord blood CD8+ T-cell effector differentiation by TGF- 1 and 4-1BB costimulation
Young-June Kim,
Teresa M. Stringfield,
Yan Chen, and
Hal E. Broxmeyer
From the Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis; the Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis; the Walther Oncology Center, Indiana University School of Medicine, Indianapolis; and the Walther Cancer Institute, Indianapolis, IN.
Transforming growth factor- 1 (TGF-1), an immunosuppressive cytokine, inhibits cytotoxic T cell (CTL) immune responses. In contrast, 4-1BB (CD137), a costimulatory molecule in the tumor necrosis factor (TNF) receptor family, amplifies CTL-mediated antitumor immune responses. We investigated whether TGF-1 responses could be reversed by 4-1BB costimulation during in vitro differentiation of naive CD8+ T cells into effector CTL cells. TGF-1 potently suppressed CTL differentiation of human cord blood naive CD8+ T cells as determined by reduced induction of characteristic phenotypes of effector cells and cytotoxic activity. TGF-1-mediated suppression of CTL differentiation was abrogated by 4-1BB costimulation but not by CD28 or another member in the TNF receptor family, CD30. 4-1BB costimulation suppressed Smad2 phosphorylation induced by TGF-1, suggesting that 4-1BB effects were at the level of TGF-1 signaling. 4-1BB effects on the TGF-1-mediated suppression were enhanced by interleukin 12 (IL-12) but counteracted by IL-4; 4-1BB expression was up- or down-regulated, respectively, by IL-12 and IL-4. IL-4 was more dominant than IL-12 when both cytokines were present during 4-1BB costimulation in the presence of TGF-1. This indicates critical roles for IL-4 and IL-12 in regulating 4-1BB effects on TGF-1-mediated suppression. (Blood. 2005;105:274-281)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y.-J. Kim, M.-K. Han, and H. E. Broxmeyer
4-1BB regulates NKG2D costimulation in human cord blood CD8+ T cells
Blood,
February 1, 2008;
111(3):
1378 - 1386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. G. Elpek, E. S. Yolcu, D. D. H. Franke, C. Lacelle, R.-H. Schabowsky, and H. Shirwan
Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling
J. Immunol.,
December 1, 2007;
179(11):
7295 - 7304.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-D. Park, L. Marti, J. Kurtzberg, and P. Szabolcs
In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes
Blood,
September 1, 2006;
108(5):
1770 - 1773.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
