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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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Blood 110, 1559-1569
   Abstract »    Full Text »    PDF »
Mouse Dendritic-Endothelial Cell Hybrids and 4-1BB Costimulation Elicit Antitumor Effects Mediated by Broad Antiangiogenic Immunity.
E. Ko, W. Luo, L. Peng, X. Wang, and S. Ferrone (2007)
Cancer Res. 67, 7875-7884
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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
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OX40 Costimulation Promotes Persistence of Cytomegalovirus-Specific CD8 T Cells: A CD4-Dependent Mechanism.
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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Memory CD4+ T-Lymphocyte Loss and Dysfunction during Primary Simian Immunodeficiency Virus Infection.
Y. Sun, S. R. Permar, A. P. Buzby, and N. L. Letvin (2007)
J. Virol. 81, 8009-8015
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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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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
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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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Induction of Postsurgical Tumor Immunity and T-Cell Memory by a Poorly Immunogenic Tumor.
P. Zhang, A. L. Cote, V. C. de Vries, E. J. Usherwood, and M. J. Turk (2007)
Cancer Res. 67, 6468-6476
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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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TLR3 ligand stimulates fully functional memory CD8+ T cells in the absence of CD4+ T-cell help.
S. Hervas-Stubbs, A. Olivier, F. Boisgerault, N. Thieblemont, and C. Leclerc (2007)
Blood 109, 5318-5326
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Characterization of the CCL21-mediated melanoma-specific immune responses and in situ melanoma eradication.
L. Novak, O. Igoucheva, S. Cho, and V. Alexeev (2007)
Mol. Cancer Ther. 6, 1755-1764
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Vaccinia Virus-Specific CD4+ T Cell Responses Target a Set of Antigens Largely Distinct from Those Targeted by CD8+ T Cell Responses.
M. Moutaftsi, H.-H. Bui, B. Peters, J. Sidney, S. Salek-Ardakani, C. Oseroff, V. Pasquetto, S. Crotty, M. Croft, E. J. Lefkowitz, et al. (2007)
J. Immunol. 178, 6814-6820
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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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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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Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus.
L. Jing, T. M. Chong, B. Byrd, C. L. McClurkan, J. Huang, B. T. Story, K. M. Dunkley, L. Aldaz-Carroll, R. J. Eisenberg, G. H. Cohen, et al. (2007)
J. Immunol. 178, 6374-6386
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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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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
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Therapy of Established Tumors in a Novel Murine Model Transgenic for Human Carcinoembryonic Antigen and HLA-A2 with a Combination of Anti-idiotype Vaccine and CTL Peptides of Carcinoembryonic Antigen.
A. Saha, S. K. Chatterjee, K. A. Foon, E. Celis, and M. Bhattacharya-Chatterjee (2007)
Cancer Res. 67, 2881-2892
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Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4+ T Cells Are a Consequence of Antigen Load.
J. C. Tilton, M. R. Luskin, A. J. Johnson, M. Manion, C. W. Hallahan, J. A. Metcalf, M. McLaughlin, R. T. Davey Jr., and M. Connors (2007)
J. Virol. 81, 2713-2725
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