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*
Department of Medicine, Queen Elizabeth II Medical Center, University of Western Australia, Nedlands, Western Australia;
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599; and
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia
A number of tumor studies have indicated a link between CD4 help
and the magnitude and persistence of CTL activity; however, the
mechanisms underlying this have been largely unclear. To evaluate and
determine the mechanisms by which CD4+ T cells synergize
with CD8+ T cells to prevent tumor growth, we used the
novel technique of monitoring in vivo CTL by labeling target cells with
CFSE. This approach was supported by the direct visualization of CTL
using peptide-MHC tetramers to follow tumor-specific T cells. The data
presented demonstrate that while cotransfer of Ag-specific
CD4+ T cells was not required for the generation of CTLs,
because adoptive transfer of CD8+ T cells alone was
sufficient, CD4+ T cells were required for the maintenance
of CD8+ T cell numbers. Our data suggest that there is a
correlation among the number of CD8+ T cells, in vivo CTL
function, and IFN-
production, with no evidence of a partial or
nonresponsive phenotype among tetramer-positive cells. We also show
that CD4+ T cells are required for CD8+ T cell
infiltration of the tumor.
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Y. Tanaka, S. Koido, M. Ohana, C. Liu, and J. Gong Induction of Impaired Antitumor Immunity by Fusion of MHC Class II-Deficient Dendritic Cells with Tumor Cells J. Immunol., February 1, 2005; 174(3): 1274 - 1280. [Abstract] [Full Text] [PDF]
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W. J. Simmons, M. Koneru, M. Mohindru, R. Thomas, S. Cutro, P. Singh, R. H. DeKruyff, G. Inghirami, A. J. Coyle, B. S. Kim, et al. Tim-3+ T-bet+ Tumor-Specific Th1 Cells Colocalize with and Inhibit Development and Growth of Murine Neoplasms J. Immunol., February 1, 2005; 174(3): 1405 - 1415. [Abstract] [Full Text] [PDF]
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 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]
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A. B. Kamath, J. Woodworth, X. Xiong, C. Taylor, Y. Weng, and S. M. Behar Cytolytic CD8+ T Cells Recognizing CFP10 Are Recruited to the Lung after Mycobacterium tuberculosis Infection J. Exp. Med., December 6, 2004; 200(11): 1479 - 1489. [Abstract] [Full Text] [PDF]
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P. A. Stumbles, R. Himbeck, J. A. Frelinger, E. J. Collins, R. A. Lake, and B. W. S. Robinson Cutting Edge: Tumor-Specific CTL Are Constitutively Cross-Armed in Draining Lymph Nodes and Transiently Disseminate to Mediate Tumor Regression following Systemic CD40 Activation J. Immunol., November 15, 2004; 173(10): 5923 - 5928. [Abstract] [Full Text] [PDF]
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Q. Lou, R. J. Kelleher Jr, A. Sette, J. Loyall, S. Southwood, R. B. Bankert, and S. H. Bernstein Germ line tumor-associated immunoglobulin VH region peptides provoke a tumor-specific immune response without altering the response potential of normal B cells Blood, August 1, 2004; 104(3): 752 - 759. [Abstract] [Full Text] [PDF]
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Y. Tanaka, S. Koido, J. Xia, M. Ohana, C. Liu, G. M. Cote, D. B. Sawyer, S. Calderwood, and J. Gong Development of Antigen-Specific CD8+ CTL in MHC Class I-Deficient Mice through CD4 to CD8 Conversion J. Immunol., June 15, 2004; 172(12): 7848 - 7858. [Abstract] [Full Text] [PDF]
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M. A. Lyman, S. Aung, J. A. Biggs, and L. A. Sherman A Spontaneously Arising Pancreatic Tumor Does Not Promote the Differentiation of Naive CD8+ T Lymphocytes into Effector CTL J. Immunol., June 1, 2004; 172(11): 6558 - 6567. [Abstract] [Full Text] [PDF]
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A. Bonehill, C. Heirman, S. Tuyaerts, A. Michiels, K. Breckpot, F. Brasseur, Y. Zhang, P. van der Bruggen, and K. Thielemans Messenger RNA-Electroporated Dendritic Cells Presenting MAGE-A3 Simultaneously in HLA Class I and Class II Molecules J. Immunol., June 1, 2004; 172(11): 6649 - 6657. [Abstract] [Full Text] [PDF]
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M. V. Maus, B. Kovacs, W. W. Kwok, G. T. Nepom, K. Schlienger, J. L. Riley, D. Allman, T. H. Finkel, and C. H. June Extensive Replicative Capacity of Human Central Memory T Cells J. Immunol., June 1, 2004; 172(11): 6675 - 6683. [Abstract] [Full Text] [PDF]
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K. L. Laurie, N. L. La Gruta, N. Koch, I. R. van Driel, and P. A. Gleeson Thymic Expression of a Gastritogenic Epitope Results in Positive Selection of Self-Reactive Pathogenic T Cells J. Immunol., May 15, 2004; 172(10): 5994 - 6002. [Abstract] [Full Text] [PDF]
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E. H. Slager, C. E. van der Minne, M. Kruse, D. D. Krueger, M. Griffioen, and S. Osanto Identification of Multiple HLA-DR-Restricted Epitopes of the Tumor-Associated Antigen CAMEL by CD4+ Th1/Th2 Lymphocytes J. Immunol., April 15, 2004; 172(8): 5095 - 5102. [Abstract] [Full Text] [PDF]
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H. L. Hanson, S. S. Kang, L. A. Norian, K. Matsui, L. A. O'Mara, and P. M. Allen CD4-Directed Peptide Vaccination Augments an Antitumor Response, but Efficacy Is Limited by the Number of CD8+ T Cell Precursors J. Immunol., April 1, 2004; 172(7): 4215 - 4224. [Abstract] [Full Text] [PDF]
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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]
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K. Chamoto, T. Tsuji, H. Funamoto, A. Kosaka, J. Matsuzaki, T. Sato, H. Abe, K. Fujio, K. Yamamoto, T. Kitamura, et al. Potentiation of Tumor Eradication by Adoptive Immunotherapy with T-cell Receptor Gene-Transduced T-Helper Type 1 Cells Cancer Res., January 1, 2004; 64(1): 386 - 390. [Abstract] [Full Text] [PDF]
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R. S. Goldszmid, J. Idoyaga, A. I. Bravo, R. Steinman, J. Mordoh, and R. Wainstok Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma J. Immunol., December 1, 2003; 171(11): 5940 - 5947. [Abstract] [Full Text] [PDF]
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A. S. Lonsdorf, H. Kuekrek, B. V. Stern, B. O. Boehm, P. V. Lehmann, and M. Tary-Lehmann Intratumor CpG-Oligodeoxynucleotide Injection Induces Protective Antitumor T Cell Immunity J. Immunol., October 15, 2003; 171(8): 3941 - 3946. [Abstract] [Full Text] [PDF]
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D. Loirat, M. Mancini-Bourgine, J.-P. Abastado, and M.-L. Michel HBsAg/HLA-A2 transgenic mice: a model for T cell tolerance to hepatitis B surface antigen in chronic hepatitis B virus infection Int. Immunol., October 1, 2003; 15(10): 1125 - 1136. [Abstract] [Full Text] [PDF]
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L. Lefrancois, A. Marzo, and K. Williams Sustained Response Initiation Is Required for T Cell Clonal Expansion But Not for Effector or Memory Development In Vivo J. Immunol., September 15, 2003; 171(6): 2832 - 2839. [Abstract] [Full Text] [PDF]
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A. Bonehill, C. Heirman, S. Tuyaerts, A. Michiels, Y. Zhang, P. van der Bruggen, and K. Thielemans Efficient Presentation of Known HLA Class II-restricted MAGE-A3 Epitopes by Dendritic Cells Electroporated with Messenger RNA Encoding an Invariant Chain with Genetic Exchange of Class II-associated Invariant Chain Peptide Cancer Res., September 1, 2003; 63(17): 5587 - 5594. [Abstract] [Full Text] [PDF]
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E. Davila, R. Kennedy, and E. Celis Generation of Antitumor Immunity by Cytotoxic T Lymphocyte Epitope Peptide Vaccination, CpG-oligodeoxynucleotide Adjuvant, and CTLA-4 Blockade Cancer Res., June 15, 2003; 63(12): 3281 - 3288. [Abstract] [Full Text] [PDF]
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J. H. Pinthus, T. Waks, K. Kaufman-Francis, D. G. Schindler, A. Harmelin, H. Kanety, J. Ramon, and Z. Eshhar Immuno-Gene Therapy of Established Prostate Tumors Using Chimeric Receptor-redirected Human Lymphocytes Cancer Res., May 15, 2003; 63(10): 2470 - 2476. [Abstract] [Full Text] [PDF]
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E. Orsini, R. Bellucci, E. P. Alyea, R. Schlossman, C. Canning, S. McLaughlin, P. Ghia, K. C. Anderson, and J. Ritz Expansion of Tumor-specific CD8+ T Cell Clones in Patients with Relapsed Myeloma after Donor Lymphocyte Infusion Cancer Res., May 15, 2003; 63(10): 2561 - 2568. [Abstract] [Full Text] [PDF]
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A. K. Nowak, R. A. Lake, A. L. Marzo, B. Scott, W. R. Heath, E. J. Collins, J. A. Frelinger, and B. W. S. Robinson Induction of Tumor Cell Apoptosis In Vivo Increases Tumor Antigen Cross-Presentation, Cross-Priming Rather than Cross-Tolerizing Host Tumor-Specific CD8 T Cells J. Immunol., May 15, 2003; 170(10): 4905 - 4913. [Abstract] [Full Text] [PDF]
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D. Stober, I. Jomantaite, R. Schirmbeck, and J. Reimann NKT Cells Provide Help for Dendritic Cell-Dependent Priming of MHC Class I-Restricted CD8+ T Cells In Vivo J. Immunol., March 1, 2003; 170(5): 2540 - 2548. [Abstract] [Full Text] [PDF]
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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]
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H. Huang, F. Li, J. R. Gordon, and J. Xiang Synergistic Enhancement of Antitumor Immunity with Adoptively Transferred Tumor-specific CD4+ and CD8+ T Cells and Intratumoral Lymphotactin Transgene Expression Cancer Res., April 1, 2002; 62(7): 2043 - 2051. [Abstract] [Full Text] [PDF]
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N. Shibagaki and M. C. Udey Dendritic Cells Transduced with Protein Antigens Induce Cytotoxic Lymphocytes and Elicit Antitumor Immunity J. Immunol., March 1, 2002; 168(5): 2393 - 2401. [Abstract] [Full Text] [PDF]
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E. L. Tham, P. Shrikant, and M. F. Mescher Activation-Induced Nonresponsiveness: A Th-Dependent Regulatory Checkpoint in the CTL Response J. Immunol., February 1, 2002; 168(3): 1190 - 1197. [Abstract] [Full Text] [PDF]
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A. Ribas, L. H. Butterfield, S. N. Amarnani, V. B. Dissette, D. Kim, W. S. Meng, G. A. Miranda, H.-J. Wang, W. H. McBride, J. A. Glaspy, et al. CD40 Cross-Linking Bypasses the Absolute Requirement for CD4 T Cells during Immunization with Melanoma Antigen Gene-modified Dendritic Cells Cancer Res., December 1, 2001; 61(24): 8787 - 8793. [Abstract] [Full Text] [PDF]
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J. Kjaergaard, L. Peng, P. A. Cohen, J. A. Drazba, A. D. Weinberg, and S. Shu Augmentation Versus Inhibition: Effects of Conjunctional OX-40 Receptor Monoclonal Antibody and IL-2 Treatment on Adoptive Immunotherapy of Advanced Tumor J. Immunol., December 1, 2001; 167(11): 6669 - 6677. [Abstract] [Full Text] [PDF]
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D. G. McNeel, L. D. Nguyen, and M. L. Disis Identification of T Helper Epitopes from Prostatic Acid Phosphatase Cancer Res., July 1, 2001; 61(13): 5161 - 5167. [Abstract] [Full Text] [PDF]
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D. W. Ju, Q. Tao, G. Lou, M. Bai, L. He, Y. Yang, and X. Cao Interleukin 18 Transfection Enhances Antitumor Immunity Induced by Dendritic Cell-Tumor Cell Conjugates Cancer Res., May 1, 2001; 61(9): 3735 - 3740. [Abstract] [Full Text]
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D. J. Nelson, S. Mukherjee, C. Bundell, S. Fisher, D. van Hagen, and B. Robinson Tumor Progression Despite Efficient Tumor Antigen Cross-Presentation and Effective "Arming" of Tumor Antigen-Specific CTL J. Immunol., May 1, 2001; 166(9): 5557 - 5566. [Abstract] [Full Text] [PDF]
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S. C. Eck and L. A. Turka Adoptive Transfer Enables Tumor Rejection Targeted against a Self-Antigen without the Induction of Autoimmunity Cancer Res., April 1, 2001; 61(7): 3077 - 3083. [Abstract] [Full Text]
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