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Science 300 (5617): 339-342

Copyright © 2003 by the American Association for the Advancement of Science

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}

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A Matter of Timing: Unsynchronized Antigen Expression and Antigen Presentation Diminish Secondary T Cell Responses.
M. Elnekave, M. Bivas-Benita, G. O. Gillard, P. Sircar, and A.-H. Hovav (2009)
J. Immunol. 183, 1013-1021
   Abstract »    Full Text »    PDF »
A Vital Role for Interleukin-21 in the Control of a Chronic Viral Infection.
J. S. Yi, M. Du, and A. J. Zajac (2009)
Science 324, 1572-1576
   Abstract »    Full Text »    PDF »
Recombinant Mycobacterium bovis BCG Prime-Recombinant Adenovirus Boost Vaccination in Rhesus Monkeys Elicits Robust Polyfunctional Simian Immunodeficiency Virus-Specific T-Cell Responses.
M. J. Cayabyab, B. Korioth-Schmitz, Y. Sun, A. Carville, H. Balachandran, A. Miura, K. R. Carlson, A. P. Buzby, B. F. Haynes, W. R. Jacobs, et al. (2009)
J. Virol. 83, 5505-5513
   Abstract »    Full Text »    PDF »
Polyfunctional CD4+ T-Cell Induction in Neutralizing Antibody-Triggered Control of Simian Immunodeficiency Virus Infection.
T. Yamamoto, N. Iwamoto, H. Yamamoto, T. Tsukamoto, T. Kuwano, A. Takeda, M. Kawada, Y. Tsunetsugu-Yokota, and T. Matano (2009)
J. Virol. 83, 5514-5524
   Abstract »    Full Text »    PDF »
Functionally Distinct LAG-3 and PD-1 Subsets on Activated and Chronically Stimulated CD8 T Cells.
J. F. Grosso, M. V. Goldberg, D. Getnet, T. C. Bruno, H.-R. Yen, K. J. Pyle, E. Hipkiss, D. A. A. Vignali, D. M. Pardoll, and C. G. Drake (2009)
J. Immunol. 182, 6659-6669
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Chronic Antigen Stimulation Alone Is Sufficient to Drive CD8+ T Cell Exhaustion.
C. M. Bucks, J. A. Norton, A. C. Boesteanu, Y. M. Mueller, and P. D. Katsikis (2009)
J. Immunol. 182, 6697-6708
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CD4+ T Cells Are Required for the Priming of CD8+ T Cells following Infection with Herpes Simplex Virus Type 1.
N. K. Rajasagi, S. H. Kassim, C. M. Kollias, X. Zhao, R. Chervenak, and S. R. Jennings (2009)
J. Virol. 83, 5256-5268
   Abstract »    Full Text »    PDF »
Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis.
T. Hayashi, S. Nagai, H. Fujii, Y. Baba, E. Ikeda, T. Kawase, and S. Koyasu (2009)
J. Immunol. 182, 6360-6368
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Cognate CD4 help is essential for the reactivation and expansion of CD8 memory T cells directed against the hematopoietic cell-specific dominant minor histocompatibility antigen, H60.
S. J. Ryu, K. M. Jung, H. S. Yoo, T. W. Kim, S. Kim, J. Chang, and E. Y. Choi (2009)
Blood 113, 4273-4280
   Abstract »    Full Text »    PDF »
Identification of a particular HIV-specific CD8+ T-cell subset with a CD27+ CD45RO-/RA+ phenotype and memory characteristics after initiation of HAART during acute primary HIV infection.
C. Lecuroux, I. Girault, A. Urrutia, J.-M. Doisne, C. Deveau, C. Goujard, L. Meyer, M. Sinet, and A. Venet (2009)
Blood 113, 3209-3217
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Recall Responses by Helpless Memory CD8+ T Cells Are Restricted by the Up-Regulation of PD-1.
S. Fuse, C.-Y. Tsai, M. J. Molloy, S. R. Allie, W. Zhang, H. Yagita, and E. J. Usherwood (2009)
J. Immunol. 182, 4244-4254
   Abstract »    Full Text »    PDF »
Characterization of the Class I-Restricted gp100 Melanoma Peptide-stimulated Primary Immune Response in Tumor-Free Vaccine-draining Lymph Nodes and Peripheral Blood.
E. B. Walker, W. Miller, D. Haley, K. Floyd, B. Curti, and W. J. Urba (2009)
Clin. Cancer Res. 15, 2541-2551
   Abstract »    Full Text »    PDF »
Postthymic maturation influences the CD8 T cell response to antigen.
L. E. Makaroff, D. W. Hendricks, R. E. Niec, and P. J. Fink (2009)
PNAS 106, 4799-4804
   Abstract »    Full Text »    PDF »
Characterization of a CD44/CD122int Memory CD8 T Cell Subset Generated under Sterile Inflammatory Conditions.
F.-M. Mbitikon-Kobo, M. Vocanson, M.-C. Michallet, M. Tomkowiak, A. Cottalorda, G. S. Angelov, C.-A. Coupet, S. Djebali, A. Marcais, B. Dubois, et al. (2009)
J. Immunol. 182, 3846-3854
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Requirement of B Cells for Generating CD4+ T Cell Memory.
J. K. Whitmire, M. S. Asano, S. M. Kaech, S. Sarkar, L. G. Hannum, M. J. Shlomchik, and R. Ahmed (2009)
J. Immunol. 182, 1868-1876
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CD8{beta} knockout mice mount normal anti-viral CD8+ T cell responses--but why?.
G. S. Angelov, P. Guillaume, and I. F. Luescher (2009)
Int. Immunol. 21, 123-135
   Abstract »    Full Text »    PDF »
S. Feau and S. P. Schoenberger (2009)
Science 323, 466-467
   Abstract »    Full Text »    PDF »

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