1. HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice.
- Author
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Fujii, Hideki, Ato, Manabu, Takahashi, Yoshimasa, Otake, Kaori, Hashimoto, Shu-ichi, Kaji, Tomohiro, Tsunetsugu-Yokota, Yasuko, Fujita, Mikako, Adachi, Akio, Nakayama, Toshinori, Taniguchi, Masaru, Koyasu, Shigeo, and Takemori, Toshitada
- Subjects
HIV ,B cells ,T cells ,ANTIGENS ,IMMUNE response ,LABORATORY mice ,DISEASE progression ,VIRAL replication ,CELL proliferation ,CYTOKINES ,GENE expression - Abstract
The viral protein Nef is a key element for the progression of HIV disease. Previous in vitro studies suggested that Nef expression in T-cell lines enhanced TCR signaling pathways upon stimulation with TCR cross-linking, leading to the proposal that Nef lowers the threshold of T-cell activation, thus increasing susceptibility to viral replication in immune response. Likewise, the in vivo effects of Nef transgenic mouse models supported T-cell hyperresponse by Nef. However, the interpretation is complicated by Nef expression early in the development of T cells in these animal models. Here, we analyzed the consequence of Nef expression in ovalbumin-specific/CD4+ peripheral T cells by using a novel mouse model and demonstrate that Nef inhibits antigen-specific T-cell proliferation and multiple functions required for immune response in vivo, which includes T-cell helper activity for the primary and memory B-cell response. However, Nef does not completely abrogate T-cell activity, as defined by low levels of cytokine production, which may afford the virus a replicative advantage. These results support a model, in which Nef expression does not cause T-cell hyperresponse in immune reaction, but instead reduces the T-cell activity, that may contribute to a low level of virus spread without viral cytopathic effects. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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