|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 January 2001, Vol. 97, No. 2, pp. 565-571
TRANSPLANTATION
Altered T-cell receptor + CD28-mediated signaling and blocked
cell cycle progression in interleukin 10 and transforming growth
factor- -treated alloreactive T cells that do not induce
graft-versus-host disease
Vassiliki A. Boussiotis,
Zong-Ming Chen,
Jay C. Zeller,
William J. Murphy,
Alla Berezovskaya,
Satwant Narula,
Maria G. Roncarolo, and
Bruce R. Blazar
From the Department of Adult Oncology, Dana-Farber
Cancer Institute, Division of Medical Oncology, Brigham and Women's
Hospital, Department of Medicine, Harvard Medical School, Boston, MA;
Department of Pediatrics, Division of Bone Marrow Transplantation,
University of Minnesota Cancer Center, Minneapolis, MN; SAIC Frederick
and the Laboratory of Leukocyte Biology, MCI-FCRDC, Frederick, MD;
Shering-Plough Research Institute, Kenilworth, NJ; and TIGET-H.S.
RAFFAELE, Milan, Italy.
The induction of anergy in T cells, although widely accepted as
critical for the maintenance of tolerance, is still poorly understood
at the molecular level. Recent evidence demonstrates that in addition
to blockade of costimulation using monoclonal antibodies (mAbs)
directed against cell surface determinants, treatment of mixed
lymphocyte reaction (MLR) cultures with interleukin 10 (IL-10)
and transforming growth factor- (TGF-) results in induction of
tolerance, rendering alloreactive murine CD4+ T cells
incapable of inducing graft-versus-host disease (GVHD) after in
vivo transfer to histoincompatible recipients. The present study, using
these cells prior to adoptive transfer, determined that
IL-10 + TGF--tolerant CD4+ T cells exhibit an altered
pattern of T-cell receptor (TCR) + CD28-mediated signaling and are
incapable of progressing out of the G1 phase of the cell
cycle during stimulation with HLA class II disparate antigen-presenting
cells. TGF + IL-10-tolerant cells were incapable of phosphorylating
TCR- , or activating ZAP-70, Ras, and MAPK, similarly to T-cell
tolerized by blockade of B7/CD28 and CD40/CD40L pathways. Moreover,
these cells were incapable of clonal expansion due to defective
synthesis of cyclin D3 and cyclin A, and defective activation of
cyclin-dependent kinase (cdk)4, cdk6, and cdk2. These cells also
exhibited defective down-regulation of p27kip1 cdk
inhibitor and lack of cyclin D2-cdk4 activation, Rb
hyperphosphorylation, and progression to the S phase of the cell cycle.
These data link anergy-specific proximal biochemical alterations and
the downstream nuclear pathways that control T-cell expansion and
provide a biochemical profile of IL-10 + TGF--tolerant
alloreactive T cells that do not induce GVHD when transferred into MHC
class II disparate recipients in vivo.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Pozo, P. Anderson, and E. Gonzalez-Rey
Induction of Alloantigen-Specific Human T Regulatory Cells by Vasoactive Intestinal Peptide
J. Immunol.,
October 1, 2009;
183(7):
4346 - 4359.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Broderick and R. B. Bankert
Membrane-Associated TGF-beta1 Inhibits Human Memory T Cell Signaling in Malignant and Nonmalignant Inflammatory Microenvironments.
J. Immunol.,
September 1, 2006;
177(5):
3082 - 3088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. R Blazar and W. J Murphy
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD)
Phil Trans R Soc B,
September 29, 2005;
360(1461):
1747 - 1767.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Waiczies, T. Prozorovski, C. Infante-Duarte, A. Hahner, O. Aktas, O. Ullrich, and F. Zipp
Atorvastatin Induces T Cell Anergy via Phosphorylation of ERK1
J. Immunol.,
May 1, 2005;
174(9):
5630 - 5635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Sturm, A Z A Leite, S Danese, K A Krivacic, G A West, S Mohr, J W Jacobberger, and C Fiocchi
Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis
Gut,
November 1, 2004;
53(11):
1624 - 1631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. E. Spaner
Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells
J. Leukoc. Biol.,
August 1, 2004;
76(2):
338 - 351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Jung, J. E. Foley, A. A. Erdmann, M. A. Eckhaus, and D. H. Fowler
CD3/CD28-costimulated T1 and T2 subsets: differential in vivo allosensitization generates distinct GVT and GVHD effects
Blood,
November 1, 2003;
102(9):
3439 - 3446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Elhalel, J.-H. Huang, W. Schmidt, J. Rachmilewitz, and M. L. Tykocinski
CTLA-4 {middle dot} FasL Induces Alloantigen-Specific Hyporesponsiveness
J. Immunol.,
June 15, 2003;
170(12):
5842 - 5850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Rutella, L. Pierelli, G. Bonanno, S. Sica, F. Ameglio, E. Capoluongo, A. Mariotti, G. Scambia, G. d'Onofrio, and G. Leone
Role for granulocyte colony-stimulating factor in the generation of human T regulatory type 1 cells
Blood,
September 18, 2002;
100(7):
2562 - 2571.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Bollard, C. Rossig, M. J. Calonge, M. H. Huls, H.-J. Wagner, J. Massague, M. K. Brenner, H. E. Heslop, and C. M. Rooney
Adapting a transforming growth factor beta -related tumor protection strategy to enhance antitumor immunity
Blood,
May 1, 2002;
99(9):
3179 - 3187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
