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The Journal of Immunology, 2007, 179: 8243-8251.
Copyright © 2007 by The American Association of Immunologists, Inc.

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CD4 T Cells Are Required for CD8 T Cell Survival during Both Primary and Memory Recall Responses1

Patricia Novy{dagger}, Michael Quigley{dagger}, Xiaopei Huang* and Yiping Yang2,*,{dagger}

* Department of Medicine and {dagger} Department Immunology, Duke University Medical Center, Durham, NC 27710

The role of CD4 T cell help in primary and secondary CD8 T cell responses to infectious pathogens remains incompletely defined. The primary CD8 T response to infections was initially thought to be largely independent of CD4 T cells, but it is not clear why some primary, pathogen-specific CD8 T cell responses are CD4 T cell dependent. Furthermore, although the generation of functional memory CD8 T cells is CD4 T cell help dependent, it remains controversial when the "help" is needed. In this study, we demonstrated that CD4 T cell help was not needed for the activation and effector differentiation of CD8 T cells during the primary response to vaccinia virus infection. However, the activated CD8 T cells showed poor survival without CD4 T cell help, leading to a reduction in clonal expansion and a diminished, but stable CD8 memory pool. In addition, we observed that CD4 T cell help provided during both the primary and secondary responses was required for the survival of memory CD8 T cells during recall expansion. Our study indicates that CD4 T cells play a crucial role in multiple stages of CD8 T cell response to vaccinia virus infection and may help to design effective vaccine strategies.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by National Institutes of Health Grants CA111807 and CA047741 (to Y.Y.), and an Alliance for Cancer Gene Therapy Grant (to Y.Y.).

2 Address correspondence and reprint requests to Dr. Yiping Yang, Departments of Medicine and Immunology, Duke University Medical Center, Box 103005, Durham, NC 27710. E-mail address: yang0029{at}mc.duke.edu

3 Abbreviations used in this paper: DC, dendritic cell; VV, vaccinia virus; WT, wild type; HA, hemagglutinin; MFI, mean fluorescence intensity; AICD, activation-induced cell death; LCMV, lymphocytic choriomeningitis virus; LN, lymph node.




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D. M. Koelle, A. Magaret, C. L. McClurkan, M. L. Remington, T. Warren, F. Teofilovici, and A. Wald
Phase I Dose-Escalation Study of a Monovalent Heat Shock Protein 70-Herpes Simplex Virus Type 2 (HSV-2) Peptide-Based Vaccine Designed To Prime or Boost CD8 T-Cell Responses in HSV-Naive and HSV-2-Infected Subjects
Clin. Vaccine Immunol., May 1, 2008; 15(5): 773 - 782.
[Abstract] [Full Text] [PDF]




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