| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Immunology and Division of Oncology, University of Washington, Seattle, WA 98195; and
Fred Hutchinson Cancer Research Center, Seattle, WA 98109
Transgenic (TG) mice were generated selectively expressing the gag protein of Friend murine leukemia virus (FMuLV) in the liver. FMuLVgag is also expressed by the FBL leukemia, and is the immunodominant tumor Ag of the CD8+ T cell response in C57BL/6 mice. gag-TG mice expressing FMuLVgag in the liver were tolerant to the protein and failed to generate a CTL response to either FBL or FMuLVgag. This tolerance reflected anergy rather than deletion, as CTL responsiveness could be recovered after four cycles of in vitro stimulation. Adoptively transferred gag-specific T cells were not anergized in gag-TG recipients, as revealed by antitumor activity in vivo. Also, such T cells did not induce detectable autoimmune injury in gag-TG liver cells. These results suggest that the requirements for a tissue Ag to provide a tolerizing stimulus are distinct from those for being the target of a T cell-mediated autoimmune response and that the requirements for induction and maintenance of peripheral tolerance are distinct for naive and primed T cells. That anergic T cells reactive with tumor-associated Ags can be recovered by repetitive in vitro stimulation and can mediate tumor therapy suggests strategies that use such Ags to generate CTL for adoptive immunotherapy should be further developed.
This article has been cited by other articles:
|
|
 |
|
  H. Conrad, K. Gebhard, H. Kronig, J. Neudorfer, D. H. Busch, C. Peschel, and H. Bernhard CTLs Directed against HER2 Specifically Cross-React with HER3 and HER4 J. Immunol., June 15, 2008; 180(12): 8135 - 8145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weinhold, D. Sommermeyer, W. Uckert, and T. Blankenstein Dual T Cell Receptor Expressing CD8+ T Cells with Tumor- and Self-Specificity Can Inhibit Tumor Growth without Causing Severe Autoimmunity J. Immunol., October 15, 2007; 179(8): 5534 - 5542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Morimoto, X. Tan, R. M. Teague, C. Ohlen, and P. D. Greenberg Induction of Tolerance in CD8+ T Cells to a Transgenic Autoantigen Expressed in the Liver Does Not Require Cross-Presentation J. Immunol., June 1, 2007; 178(11): 6849 - 6860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Knutson, C. J. Krco, C. L. Erskine, K. Goodman, L. E. Kelemen, P. J. Wettstein, P. S. Low, L. C. Hartmann, and K. R. Kalli T-Cell Immunity to the Folate Receptor Alpha Is Prevalent in Women With Breast or Ovarian Cancer J. Clin. Oncol., September 10, 2006; 24(26): 4254 - 4261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Ryan and T. D. Schell Accumulation of CD8+ T Cells in Advanced-Stage Tumors and Delay of Disease Progression following Secondary Immunization against an Immunorecessive Epitope J. Immunol., July 1, 2006; 177(1): 255 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Ercolini, B. H. Ladle, E. A. Manning, L. W. Pfannenstiel, T. D. Armstrong, J.-P. H. Machiels, J. G. Bieler, L. A. Emens, R. T. Reilly, and E. M. Jaffee Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response J. Exp. Med., May 16, 2005; 201(10): 1591 - 1602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. O'Mara, L. A. Norian, D. Kreamalmeyer, J. M. White, and P. M. Allen T Cell-Mediated Delay of Spontaneous Mammary Tumor Onset: Increased Efficacy with In Vivo versus In Vitro Activation J. Immunol., April 15, 2005; 174(8): 4662 - 4669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Mihalyo, A. D. H. Doody, J. P. McAleer, E. C. Nowak, M. Long, Y. Yang, and A. J. Adler In Vivo Cyclophosphamide and IL-2 Treatment Impedes Self-Antigen-Induced Effector CD4 Cell Tolerization: Implications for Adoptive Immunotherapy J. Immunol., May 1, 2004; 172(9): 5338 - 5345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Friedman, C. S. Bangur, E. J. Zasloff, L. Fan, T. Wang, Y. Watanabe, and M. Kalos Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen J. Immunol., March 1, 2004; 172(5): 3319 - 3327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. O'Mara and P. M. Allen Pulmonary Tumors Inefficiently Prime Tumor-Specific T Cells J. Immunol., January 1, 2004; 172(1): 310 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, W. Li, S. Liang, D. Cai, M. P. Kieny, L. Jacob, A. Linnenbach, J. W. Abramczuk, H. Bender, K. Sproesser, et al. Recombinant CD63/ME491/Neuroglandular/NKI/C-3 Antigen Inhibits Growth of Established Tumors in Transgenic Mice J. Immunol., September 15, 2003; 171(6): 2922 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Higgins, M. A. Mihalyo, and A. J. Adler Effector CD4 Cells Are Tolerized Upon Exposure to Parenchymal Self-Antigen J. Immunol., October 1, 2002; 169(7): 3622 - 3629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Hural, R. S. Friedman, A. McNabb, S. S. Steen, R. A. Henderson, and M. Kalos Identification of Naturally Processed CD4 T Cell Epitopes from the Prostate-Specific Antigen Kallikrein 4 Using Peptide-Based In Vitro Stimulation J. Immunol., July 1, 2002; 169(1): 557 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ohlen, M. Kalos, L. E. Cheng, A. C. Shur, D. J. Hong, B. D. Carson, N. C.T. Kokot, C. G. Lerner, B. D. Sather, E. S. Huseby, et al. CD8+ T Cell Tolerance to a Tumor-associated Antigen Is Maintained at the Level of Expansion Rather than Effector Function J. Exp. Med., June 3, 2002; 195(11): 1407 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Riddell Progress in cancer vaccines by enhanced self-presentation PNAS, July 31, 2001; 98(16): 8933 - 8935. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
