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Science 11 April 2003:
Vol. 300. no. 5617, pp. 339 - 342
DOI: 10.1126/science.1083317
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Reports

Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help

Joseph C. Sun, Michael J. Bevan*

The CD8+ cytotoxic T cell response to pathogens is thought to be CD4+ helper T cell independent because infectious agents provide their own inflammatory signals. Mice that lack CD4+ T cells mount a primary CD8 response to Listeria monocytogenes equal to that of wild-type mice and rapidly clear the infection. However, protective memory to a challenge is gradually lost in the former animals. Memory CD8+ T cells from normal mice can respond rapidly, but memory CD8+ T cells that are generated without CD4 help are defective in their ability to respond to secondary encounters with antigen. The results highlight a previously undescribed role for CD4 help in promoting protective CD8 memory development.

Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
*   To whom correspondence should be addressed: E-mail: mbevan{at}u.washington.edu

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Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells.
A. M. Intlekofer, N. Takemoto, C. Kao, A. Banerjee, F. Schambach, J. K. Northrop, H. Shen, E. J. Wherry, and S. L. Reiner (2007)
J. Exp. Med. 204, 2015-2021
   Abstract »    Full Text »    PDF »
Role of Human Immunodeficiency Virus (HIV)-Specific T-Cell Immunity in Control of Dual HIV-1 and HIV-2 Infection.
N. N. Zheng, M. J. McElrath, P.-S. Sow, S. E. Hawes, H. Diallo-Agne, J. E. Stern, F. Li, A. L. Mesher, A. D. Robinson, G. S. Gottlieb, et al. (2007)
J. Virol. 81, 9061-9071
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CD8+ T Cell-Mediated Airway Hyperresponsiveness and Inflammation Is Dependent on CD4+IL-4+ T Cells.
T. Koya, N. Miyahara, K. Takeda, S. Matsubara, H. Matsuda, C. Swasey, A. Balhorn, A. Dakhama, and E. W. Gelfand (2007)
J. Immunol. 179, 2787-2796
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Tumors Hamper the Immunogenic Competence of CD4+ T Cell-Directed Dendritic Cell Vaccination.
V. S. Zimmermann, A. Casati, C. Schiering, S. Caserta, R. Hess Michelini, V. Basso, and A. Mondino (2007)
J. Immunol. 179, 2899-2909
   Abstract »    Full Text »    PDF »
Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non genotype 1 infection.
J. Schulze zur Wiesch, G. M. Lauer, J. Timm, T. Kuntzen, M. Neukamm, A. Berical, A. M. Jones, B. E. Nolan, S. A. Longworth, V. Kasprowicz, et al. (2007)
Blood 110, 1559-1569
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Multiple-Cytokine-Producing Antiviral CD4 T Cells Are Functionally Superior to Single-Cytokine-Producing Cells.
S. Kannanganat, C. Ibegbu, L. Chennareddi, H. L. Robinson, and R. R. Amara (2007)
J. Virol. 81, 8468-8476
   Abstract »    Full Text »    PDF »
Induction of CD4-Independent E7-Specific CD8+ Memory Response by Heat Shock Fusion Protein.
H. Liu, B. H. Wu, G. J. Rowse, and P. C. R. Emtage (2007)
Clin. Vaccine Immunol. 14, 1013-1023
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Direct Ex Vivo Analyses of HLA-DR1 Transgenic Mice Reveal an Exceptionally Broad Pattern of Immunodominance in the Primary HLA-DR1-Restricted CD4 T-Cell Response to Influenza Virus Hemagglutinin.
K. A. Richards, F. A. Chaves, F. R. Krafcik, D. J. Topham, C. A. Lazarski, and A. J. Sant (2007)
J. Virol. 81, 7608-7619
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The Antiviral CD8+ T Cell Response Is Differentially Dependent on CD4+ T Cell Help Over the Course of Persistent Infection.
C. C. Kemball, C. D. Pack, H. M. Guay, Z.-N. Li, D. A. Steinhauer, E. Szomolanyi-Tsuda, and A. E. Lukacher (2007)
J. Immunol. 179, 1113-1121
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Protection from Lethal Infection by Adoptive Transfer of CD8 T Cells Genetically Engineered to Express Virus-Specific Innate Immune Receptor.
K. Iizuka, C. Nakajima, Y.-M. Iizuka, M. Takase, T. Kato, S. Noda, K. Tanaka, and O. Kanagawa (2007)
J. Immunol. 179, 1122-1128
   Abstract »    Full Text »    PDF »
Memory CD4 T Cells Enhance Primary CD8 T-Cell Responses.
C. M. Krawczyk, H. Shen, and E. J. Pearce (2007)
Infect. Immun. 75, 3556-3560
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Disparate Primary and Secondary Allospecific CD8+ T Cell Cytolytic Effector Function in the Presence or Absence of Host CD4+ T Cells.
P. H. Horne, M. A. Koester, K. Jayashankar, K. E. Lunsford, H. L. Dziema, and G. L. Bumgardner (2007)
J. Immunol. 179, 80-88
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Rapid and sustained CD4+ T-cell-independent immunity from adenovirus-encoded vaccine antigens.
P. J. Holst, C. Bartholdy, A. Stryhn, A. R. Thomsen, and J. P. Christensen (2007)
J. Gen. Virol. 88, 1708-1716
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Recognition of Prostate and Melanoma Tumor Cells by Six-Transmembrane Epithelial Antigen of Prostate-Specific Helper T Lymphocytes in a Human Leukocyte Antigen Class II-Restricted Manner.
H. Kobayashi, T. Nagato, K. Sato, N. Aoki, S. Kimura, M. Murakami, H. Iizuka, M. Azumi, H. Kakizaki, M. Tateno, et al. (2007)
Cancer Res. 67, 5498-5504
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Early Virus-Associated Bystander Events Affect the Fitness of the CD8 T Cell Response to Persistent Virus Infection.
N. P. Andrews, C. D. Pack, V. Vezys, G. N. Barber, and A. E. Lukacher (2007)
J. Immunol. 178, 7267-7275
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PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors.
J.-Y. Zhang, Z. Zhang, X. Wang, J.-L. Fu, J. Yao, Y. Jiao, L. Chen, H. Zhang, J. Wei, L. Jin, et al. (2007)
Blood 109, 4671-4678
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Requirement for CD4 T Cell Help in Maintenance of Memory CD8 T Cell Responses Is Epitope Dependent.
E. A. Ramsburg, J. M. Publicover, D. Coppock, and J. K. Rose (2007)
J. Immunol. 178, 6350-6358
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MHC Class II-Transduced Tumor Cells Originating in the Immune-Privileged Eye Prime and Boost CD4+ T Lymphocytes that Cross-react with Primary and Metastatic Uveal Melanoma Cells.
J. J. Bosch, J. A. Thompson, M. K. Srivastava, U. K. Iheagwara, T. G. Murray, M. Lotem, B. R. Ksander, and S. Ostrand-Rosenberg (2007)
Cancer Res. 67, 4499-4506
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Th1 and Th2 Cells Help CD8 T-Cell Responses.
M. J. Ekkens, D. J. Shedlock, E. Jung, A. Troy, E. L. Pearce, H. Shen, and E. J. Pearce (2007)
Infect. Immun. 75, 2291-2296
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Cutting Edge: Recombinant Listeria monocytogenes Expressing a Single Immune-Dominant Peptide Confers Protective Immunity to Herpes Simplex Virus-1 Infection.
M. T. Orr, N. N. Orgun, C. B. Wilson, and S. S. Way (2007)
J. Immunol. 178, 4731-4735
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Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7R{alpha}-expressing cells.
H. Dooms, K. Wolslegel, P. Lin, and A. K. Abbas (2007)
J. Exp. Med. 204, 547-557
   Abstract »    Full Text »    PDF »


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