Pike, R.; (2011) The role of CD4+ T cells in Friend virus infection. Doctoral thesis , UCL (University College London).

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Abstract

Retroviruses can establish persistent infection despite induction of a multipartite antiviral immune response. Whether collective failure of all parts of the immune response or selective deficiency in one crucial part underlies the inability of the host to clear retroviral infections is currently uncertain. In this study, the contribution of virus-specific CD4+ T cells in resistance against Friend virus (FV) infection in the murine host is examined. The results show that the magnitude and duration of the FV-specific CD4+ T cell response is directly proportional to resistance against acute FV infection and subsequent disease. Notably, significant protection against FV-induced disease is afforded by FV-specific CD4+ T cells in the absence of a virus-specific CD8+ T cell or B cell response. Enhanced spread of FV infection in hosts with increased genetic susceptibility causes a proportional increase in the number of FV-specific CD4+ T cells required to control FV-induced disease. Thus, these results suggest that FV-specific CD4+ T cells provide significant direct protection against acute FV infection, the extent of which critically depends on the ratio of FV-infected cells to FV-specific CD4+ T cells. In addition to precursor frequency, the T cell receptor (TCR) affinity for antigen is also considered an important contributor to CD4+ T cell expansion and effector function. Study of polyclonal TCRβ-transgenic FV-specific CD4+ T cells has previously revealed a distinct pattern of clonal evolution during FV infection. In the current study, immunisation regimens, including adjuvanted peptide and replication-attenuated retrovirus vaccination, are assessed for the overall TCR affinity of the CD4+ T cell population they elicit. The implications for vaccine design and vaccine-induced CD4+ T cell-mediated protection are discussed.

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