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* Department of Medicine and
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.
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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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