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Science 11 April 2003:
Vol. 300. no. 5617, pp. 337 - 339
DOI: 10.1126/science.1082305
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Reports

Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory

Devon J. Shedlock, Hao Shen*

Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4-/- hosts, whereas memory CD8 cells generated in CD4-/- mice mounted defective recall responses in CD4+/+ adoptive hosts. These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory.

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
*   To whom correspondence should be addressed at the Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA. E-mail: hshen{at}mail.med.upenn.edu

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J. Immunol. 179, 4529-4534
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J. Immunol. 179, 2899-2909
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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)
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J. Virol. 81, 8468-8476
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I. R. Humphreys, A. Loewendorf, C. de Trez, K. Schneider, C. A. Benedict, M. W. Munks, C. F. Ware, and M. Croft (2007)
J. Immunol. 179, 2195-2202
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Y. Sun, S. R. Permar, A. P. Buzby, and N. L. Letvin (2007)
J. Virol. 81, 8009-8015
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H. Liu, B. H. Wu, G. J. Rowse, and P. C. R. Emtage (2007)
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J. Immunol. 179, 1113-1121
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J. Immunol. 179, 1122-1128
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P. Zhang, A. L. Cote, V. C. de Vries, E. J. Usherwood, and M. J. Turk (2007)
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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.
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J. Immunol. 179, 80-88
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J. Immunol. 178, 7267-7275
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E. A. Ramsburg, J. M. Publicover, D. Coppock, and J. K. Rose (2007)
J. Immunol. 178, 6350-6358
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J. Immunol. 178, 6374-6386
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J. Immunol. 178, 2787-2793
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P. Sinai, R. E. Berg, J. M. Haynie, M. J. Egorin, R. L. Ilaria Jr, and J. Forman (2007)
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C. Bartholdy, S. O. Kauffmann, J. P. Christensen, and A. R. Thomsen (2007)
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J. Immunol. 178, 778-787
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J. Gen. Virol. 88, 217-225
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IL-12-Programmed Long-Term CD8+ T Cell Responses Require STAT4.
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Y. Sun, J. E. Schmitz, A. P. Buzby, B. R. Barker, S. S. Rao, L. Xu, Z.-y. Yang, J. R. Mascola, G. J. Nabel, and N. L. Letvin (2006)
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Prime-Boost with Alternating DNA Vaccines Designed to Engage Different Antigen Presentation Pathways Generates High Frequencies of Peptide-Specific CD8+ T Cells.
J. N. Radcliffe, J. S. Roddick, P. S. Friedmann, F. K. Stevenson, and S. M. Thirdborough (2006)
J. Immunol. 177, 6626-6633
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L. Viollet, V. Monceaux, F. Petit, R. H. T. Fang, M.-C. Cumont, B. Hurtrel, and J. Estaquier (2006)
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J. Immunol. 177, 6122-6128
   Abstract »    Full Text »    PDF »
Adoptive Transfer of Vaccine-Induced Peripheral Blood Mononuclear Cells to Patients with Metastatic Melanoma following Lymphodepletion.
D. J. Powell Jr., M. E. Dudley, K. A. Hogan, J. R. Wunderlich, and S. A. Rosenberg (2006)
J. Immunol. 177, 6527-6539
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Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection.
E. M. M. van Leeuwen, E. B. M. Remmerswaal, M. H. M. Heemskerk, I. J. M. ten Berge, and R. A. W. van Lier (2006)
Blood 108, 3121-3127
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Organ- and Disease-Stage-Specific Regulation of Toxoplasma gondii-Specific CD8-T-Cell Responses by CD4 T Cells..
S. Lutjen, S. Soltek, S. Virna, M. Deckert, and D. Schluter (2006)
Infect. Immun. 74, 5790-5801
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Impaired Memory CD8 T Cell Development in the Absence of Methyl-CpG-Binding Domain Protein 2.
E. N. Kersh (2006)
J. Immunol. 177, 3821-3826
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