| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104; and
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, 60637
Recent studies of T cell anergy induction have produced conflicting conclusions as to the role of the negative regulatory receptor, CTLA-4. Several in vivo models of tolerance have implicated the interaction of CTLA-4 and its ligands, B7.1 and B7.2, as an essential step in induction of anergy, while results from a number of other systems have indicated that signals from the TCR/CD3 complex alone are sufficient to induce T cell unresponsiveness. One explanation for this disparity is that the requirements for anergy induction depend closely on the details of the system: in vivo vs in vitro, route of stimulus administration, naive vs memory cells, CD4+ vs CD8+ cells, etc. To test this possibility, we established an in vivo anergy model using mice transgenic for the 2C TCR on a recombination-activating gene-2-deficient background, that either express or lack the CTLA-4 molecule. This system provides us with a very homogeneous pool of naive Ag-specific CD8+ T cells, allowing us to control some of the conditions mentioned above. We found that T cells from CTLA-4-deficient mice were anergized by injections of soluble antigenic peptide as efficiently as were CTLA-4-expressing cells. These results indicate that CTLA-4 is not universally required for in vivo T cell anergy induction and may point to distinctions between regulation of peripheral tolerance in CD4+ and CD8+ T cells.
This article has been cited by other articles:
|
|
 |
|
  S. K. Dalai, S. Mirshahidi, A. Morrot, F. Zavala, and S. Sadegh-Nasseri Anergy in Memory CD4+ T Cells Is Induced by B Cells J. Immunol., September 1, 2008; 181(5): 3221 - 3231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Srinivasan and K. A. Frauwirth Reciprocal NFAT1 and NFAT2 Nuclear Localization in CD8+ Anergic T Cells Is Regulated by Suboptimal Calcium Signaling J. Immunol., September 15, 2007; 179(6): 3734 - 3741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pandiyan, J. K. E. Hegel, M. Krueger, D. Quandt, and M. C. Brunner-Weinzierl High IFN-{gamma} Production of Individual CD8 T Lymphocytes Is Controlled by CD152 (CTLA-4) J. Immunol., February 15, 2007; 178(4): 2132 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gattinoni, A. Ranganathan, D. R. Surman, D. C. Palmer, P. A. Antony, M. R. Theoret, D. M. Heimann, S. A. Rosenberg, and N. P. Restifo CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent Blood, December 1, 2006; 108(12): 3818 - 3823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. E. Brown, C. Blank, J. Kline, A. K. Kacha, and T. F. Gajewski Homeostatic Proliferation as an Isolated Variable Reverses CD8+ T Cell Anergy and Promotes Tumor Rejection J. Immunol., October 1, 2006; 177(7): 4521 - 4529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Zhang, S. Yu, D. Calida, Z. Zhao, B. Gran, M. Kamoun, and A. Rostami Loss of the Surface Antigen 3G11 Characterizes a Distinct Population of Anergic/Regulatory T Cells in Experimental Autoimmune Encephalomyelitis J. Immunol., March 15, 2006; 176(6): 3366 - 3373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mukherjee, A. Ahmed, and D. Nandi CTLA4-CD80/CD86 interactions on primary mouse CD4+ T cells integrate signal-strength information to modulate activation with Concanavalin A J. Leukoc. Biol., July 1, 2005; 78(1): 144 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Inobe and R. H. Schwartz CTLA-4 Engagement Acts as a Brake on CD4+ T Cell Proliferation and Cytokine Production but Is Not Required for Tuning T Cell Reactivity in Adaptive Tolerance J. Immunol., December 15, 2004; 173(12): 7239 - 7248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. F. Rowley and A. Al-Shamkhani Stimulation by Soluble CD70 Promotes Strong Primary and Secondary CD8+ Cytotoxic T Cell Responses In Vivo J. Immunol., May 15, 2004; 172(10): 6039 - 6046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Vacchio and R. J. Hodes CD28 Costimulation Is Required for In Vivo Induction of Peripheral Tolerance in CD8 T Cells J. Exp. Med., January 6, 2003; 197(1): 19 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mukherjee, P. K. Maiti, and D. Nandi Role of CD80, CD86, and CTLA4 on mouse CD4+ T lymphocytes in enhancing cell-cycle progression and survival after activation with PMA and ionomycin J. Leukoc. Biol., November 1, 2002; 72(5): 921 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sho, A. Yamada, N. Najafian, A. D. Salama, H. Harada, S. E. Sandner, A. Sanchez-Fueyo, X. X. Zheng, T. B. Strom, and M. H. Sayegh Physiological Mechanisms of Regulating Alloimmunity: Cytokines, CTLA-4, CD25+ Cells, and the Alloreactive T Cell Clone Size J. Immunol., October 1, 2002; 169(7): 3744 - 3751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Hwang, W. B. Sweatt, I. E. Brown, C. Blank, T. F. Gajewski, J. A. Bluestone, and M.-L. Alegre Cutting Edge: Targeted Ligation of CTLA-4 In Vivo by Membrane-Bound Anti-CTLA-4 Antibody Prevents Rejection of Allogeneic Cells J. Immunol., July 15, 2002; 169(2): 633 - 637. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
