|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 June 2002, Vol. 99, No. 12, pp. 4509-4516
IMMUNOBIOLOGY
The lymphoproliferative defect in
CTLA-4-deficient mice is ameliorated by
an inhibitory NK cell receptor
Cynthia A. Chambers,
Joonsoo Kang,
Yongjian Wu,
Werner Held,
David H. Raulet, and
James P. Allison
From the Department of Pathology, University of
Massachusetts Medical School, Worcester; Department of Neurobiology,
Stanford University, Palo Alto, CA; Ludwig Institute for Cancer
Research, Lausanne, Switzerland; Division of Immunology, Department of
Molecular and Cellular Biology, Cancer Research Laboratory, Howard
Hughes Research Institute, University of California, Berkeley.
T-cell responses are regulated by activating and inhibiting
signals. CD28 and its homologue, cytotoxic T-lymphocyte antigen 4 (CTLA-4), are the primary regulatory molecules that enhance or
inhibit T-cell activation, respectively. Recently it has been shown
that inhibitory natural killer (NK) cell receptors (NKRs) are expressed
on subsets of T cells. It has been proposed that these receptors may
also play an important role in regulating T-cell responses. However,
the extent to which the NKRs modulate peripheral T-cell homeostasis and
activation in vivo remains unclear. In this report we show that NK cell
inhibitory receptor Ly49A engagement on T cells dramatically limits
T-cell activation and the resultant lymphoproliferative disorder that
occurs in CTLA-4-deficient mice. Prevention of activation and
expansion of the potentially autoreactive CTLA-4 / T
cells by the Ly49A-mediated inhibitory signal demonstrates that NKR
expression can play an important regulatory role in T-cell homeostasis
in vivo. These results demonstrate the importance of inhibitory signals
in T-cell homeostasis and suggest the common biochemical basis of
inhibitory signaling pathways in T lymphocytes.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. J. Engelhardt, T. J. Sullivan, and J. P. Allison
CTLA-4 Overexpression Inhibits T Cell Responses through a CD28-B7-Dependent Mechanism
J. Immunol.,
July 15, 2006;
177(2):
1052 - 1061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Smith, T. Patterson, and M. E. Pauza
Transgenic Ly-49A Inhibits Antigen-Driven T Cell Activation and Delays Diabetes
J. Immunol.,
April 1, 2005;
174(7):
3897 - 3905.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Saurer, I. Seibold, C. Vallan, W. Held, and C. Mueller
Cutting Edge: Stimulation with the Cognate Self-Antigen Induces Expression of the Ly49A Receptor on Self-Reactive T Cells Which Modulates Their Responsiveness
J. Immunol.,
December 15, 2003;
171(12):
6334 - 6338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Vasu, S. R. Gorla, B. S. Prabhakar, and M. J. Holterman
Targeted engagement of CTLA-4 prevents autoimmune thyroiditis
Int. Immunol.,
May 1, 2003;
15(5):
641 - 654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
