Assessing the function of EBV-specific CD4\(^+\) T cells

Meckiff, Benjamin James (2014). Assessing the function of EBV-specific CD4\(^+\) T cells. University of Birmingham. M.Res.

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Abstract

CD4\(^+\) T cells play a key role in orchestrating an efficient immune response to viral infection; yet due to a variety of factors remain relatively poorly studied. However, recent advancements in MHC class II tetramer technology are allowing single cell analysis of CD4\(^+\) T cell responses to be studied for the first time. We sought to take advantage of these reagents in the context of the oncogenic herpesvirus EBV, in order to establish the cytokine profiles and cytotoxic potential of CD4\(^+\) T cells specific for a variety of viral epitopes. Such knowledge would help with the improvement of adoptive T cell therapies for EBV-related malignancies that have been shown to be more efficacious with higher proportions of CD4\(^+\) T cells.

Using flow cytometry we found that the EBV-specific CD4\(^+\) T cells are capable of responding to EBV-infected cells ex vivo. Using MHC class II tetramers we have demonstrated that responding cells were a heterogeneous population expressing the Th1 associated transcription factor T-bet and were polyfunctional producing IFNγ, TNFα or a combination of both. In addition we found that unmanipulated CD4\(^+\) T cells specific for EBV-derived epitopes possess cytotoxic potential \(ex\) \(vivo\).

These results may help to improve immune therapy for EBV-associated cancers.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):