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The Journal of Immunology, 2007, 178, 6350 -6358
Copyright © 2007 by The American Association of Immunologists, Inc.

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Requirement for CD4 T Cell Help in Maintenance of Memory CD8 T Cell Responses Is Epitope Dependent1

Elizabeth A. Ramsburg*, Jean M. Publicover*,{dagger}, Dagan Coppock* and John K. Rose2,*

* Department of Pathology and {dagger} Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510

CD4 Th cells play critical roles in stimulating Ab production and in generating primary or maintaining memory CTL. The requirement for CD4 help in generating and maintaining CTL responses has been reported to vary depending on the vector or method used for immunization. In this study, we examined the requirement for CD4 T cell help in generating and maintaining CTL responses to an experimental AIDS vaccine vector based on live recombinant vesicular stomatitis virus (VSV) expressing HIV Env protein. We found that primary CD8 T cell responses and short-term memory to HIV Env and VSV nucleocapsid (VSV N) proteins were largely intact in CD4 T cell-deficient mice. These responses were efficiently recalled at 30 days postinfection by boosting with vaccinia recombinants expressing HIV Env or VSV N. However, by 60 days postinfection, the memory/recall response to VSV N was lost in CD4-deficient mice, while the recall response HIV Env was partially maintained in the same animals for at least 90 days. This result indicates that there are epitope-specific requirements for CD4 help in the maintenance of memory CD8 T cell responses. Our results also suggest that choice of epitopes might be critical in an AIDS vaccine designed to protect against disease in the context of reduced or declining CD4 T cell help.

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 R37-AI40357 and R0-AI45510 and by a HIV-1 Vaccine Design and Development Team contract (NIH N01-AI-25458).

2 Address correspondence and reprint requests to Dr. John K. Rose, Department of Pathology, Yale University School of Medicine, 310 Cedar Street (LH315), New Haven, CT 06510. E-mail address: john.rose{at}yale.edu

3 Abbreviations used in this paper: VSV, vesicular stomatitis virus; VSV N, VSV nucleocapsid; RT, room temperature.




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