| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
In this report, we address whether a growing tumor provides sufficient inflammatory signals to promote activation, clonal expansion, and acquisition of effector functions by naive tumor-specific CD8+ T lymphocytes. CD8+ T lymphocytes obtained from hemagglutinin (HA)-specific clone 4 TCR-transgenic mice were injected into recipient mice that spontaneously develop pancreatic tumors expressing HA as a tumor-associated Ag (RIP-Tag2-HA mice). When 3 x 106 clone 4 CD8+ T cells were transferred into tumor-bearing mice, the cells became activated in the pancreatic lymph nodes where they proliferated and acquired effector functions such as cytolytic activity and IFN-
production. Surprisingly, reducing the number of adoptively transferred CD8+ T cells led to a parallel reduction in the proportion of the activated cells that exhibited effector functions, suggesting that CTL differentiation was induced by the large numbers of activated CD8+ T cells and not the tumor environment. Provision of tumor-specific CD4+ helper cells provided the signals required to promote both the development of CTL effector functions and increased clonal expansion, resulting in tumor eradication. Considering that only small numbers of tumor-specific CD8+ T cells would be present in a conventional T cell repertoire, these data suggest that tumor growth alone may not provide the inflammatory signals necessary to support the development of CD8+ T cell effector functions.
This article has been cited by other articles:
|
|
 |
|
  A. Bai, E. Higham, H. N. Eisen, K. D. Wittrup, and J. Chen From the Cover: Rapid tolerization of virus-activated tumor-specific CD8+ T cells in prostate tumors of TRAMP mice PNAS, September 2, 2008; 105(35): 13003 - 13008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Willimsky, M. Czeh, C. Loddenkemper, J. Gellermann, K. Schmidt, P. Wust, H. Stein, and T. Blankenstein Immunogenicity of premalignant lesions is the primary cause of general cytotoxic T lymphocyte unresponsiveness J. Exp. Med., July 7, 2008; 205(7): 1687 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Y. Gerner, K. A. Casey, and M. F. Mescher Defective MHC Class II Presentation by Dendritic Cells Limits CD4 T Cell Help for Antitumor CD8 T Cell Responses J. Immunol., July 1, 2008; 181(1): 155 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Plesa, A. E. Snook, S. A. Waldman, and L. C. Eisenlohr Derivation and Fluidity of Acutely Induced Dysfunctional CD8+ T Cells J. Immunol., April 15, 2008; 180(8): 5300 - 5308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. J. Wong, R. Bos, and L. A. Sherman Tumor-Specific CD4+ T Cells Render the Tumor Environment Permissive for Infiltration by Low-Avidity CD8+ T Cells J. Immunol., March 1, 2008; 180(5): 3122 - 3131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Long, A. M. Slaiby, S. Wu, A. T. Hagymasi, M. A. Mihalyo, S. Bandyopadhyay, A. T. Vella, and A. J. Adler Histone Acetylation at the Ifng Promoter in Tolerized CD4 Cells Is Associated with Increased IFN-{gamma} Expression during Subsequent Immunization to the Same Antigen J. Immunol., November 1, 2007; 179(9): 5669 - 5677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Chaput, G. Darrasse-Jeze, A.-S. Bergot, C. Cordier, S. Ngo-Abdalla, D. Klatzmann, and O. Azogui Regulatory T Cells Prevent CD8 T Cell Maturation by Inhibiting CD4 Th Cells at Tumor Sites J. Immunol., October 15, 2007; 179(8): 4969 - 4978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Curtsinger, M. Y. Gerner, D. C. Lins, and M. F. Mescher Signal 3 Availability Limits the CD8 T Cell Response to a Solid Tumor J. Immunol., June 1, 2007; 178(11): 6752 - 6760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Anderson, K. Shafer-Weaver, N. M. Greenberg, and A. A. Hurwitz Tolerization of Tumor-Specific T Cells Despite Efficient Initial Priming in a Primary Murine Model of Prostate Cancer J. Immunol., February 1, 2007; 178(3): 1268 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Johnson, B. Heemskerk, D. J. Powell Jr., C. J. Cohen, R. A. Morgan, M. E. Dudley, P. F. Robbins, and S. A. Rosenberg Gene Transfer of Tumor-Reactive TCR Confers Both High Avidity and Tumor Reactivity to Nonreactive Peripheral Blood Mononuclear Cells and Tumor-Infiltrating Lymphocytes J. Immunol., November 1, 2006; 177(9): 6548 - 6559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Otahal, T. D. Schell, S. C. Hutchinson, B. B. Knowles, and S. S. Tevethia Early Immunization Induces Persistent Tumor-Infiltrating CD8+ T Cells against an Immunodominant Epitope and Promotes Lifelong Control of Pancreatic Tumor Progression in SV40 Tumor Antigen Transgenic Mice. J. Immunol., September 1, 2006; 177(5): 3089 - 3099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ambrosino, M. Spadaro, M. Iezzi, C. Curcio, G. Forni, P. Musiani, W.-Z. Wei, and F. Cavallo Immunosurveillance of erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance. Cancer Res., August 1, 2006; 66(15): 7734 - 7740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. van der Most, A. Currie, B. W.S. Robinson, and R. A. Lake Cranking the Immunologic Engine with Chemotherapy: Using Context to Drive Tumor Antigen Cross-Presentation towards Useful Antitumor Immunity Cancer Res., January 15, 2006; 66(2): 601 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Garbe, B. Vermeer, J. Gamrekelashvili, R. v. Wasielewski, F. R. Greten, A. M. Westendorf, J. Buer, R. M. Schmid, M. P. Manns, F. Korangy, et al. Genetically Induced Pancreatic Adenocarcinoma Is Highly Immunogenic and Causes Spontaneous Tumor-Specific Immune Responses Cancer Res., January 1, 2006; 66(1): 508 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. F. H. M. Boonman, G. J. D. van Mierlo, M. F. Fransen, R. J. W. de Keizer, M. J. Jager, C. J. M. Melief, and R. E. M. Toes Maintenance of Immune Tolerance Depends on Normal Tissue Homeostasis J. Immunol., October 1, 2005; 175(7): 4247 - 4254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Martinez, H. T. C. Kreuwel, W. L. Redmond, R. Trenney, K. Hunter, H. Rosen, N. Sarvetnick, L. S. Wicker, and L. A. Sherman CD8+ T Cell Tolerance in Nonobese Diabetic Mice Is Restored by Insulin-Dependent Diabetes Resistance Alleles J. Immunol., August 1, 2005; 175(3): 1677 - 1685. [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. Lyman, C. T. Nugent, K. L. Marquardt, J. A. Biggs, E. G. Pamer, and L. A. Sherman The Fate of Low Affinity Tumor-Specific CD8+ T Cells in Tumor-Bearing Mice J. Immunol., March 1, 2005; 174(5): 2563 - 2572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Chen, M. J. Pittet, L. Gorelik, R. A. Flavell, R. Weissleder, H. von Boehmer, and K. Khazaie Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-{beta} signals in vivo PNAS, January 11, 2005; 102(2): 419 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhou, Z. Lu, J. D. McCadden, H. I. Levitsky, and A. L. Marson Reciprocal Changes in Tumor Antigenicity and Antigen-specific T Cell Function during Tumor Progression J. Exp. Med., December 20, 2004; 200(12): 1581 - 1592. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
