Transcriptional and migration regulation of T follicular helper cell differentiation
AuthorSheikh, Amania Anwar
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2023-06-03.
© 2021 Amania Anwar Sheikh
T follicular helper cells (TFH) are specialised CD4+ T cells that promote B cells maturation into antibody secreting plasma and memory cells. Most of the current vaccines generate protection via the induction of long-term antibody responses and circulating TFH are reliable predictors of vaccine response. Conversely, dysfunctional TFH cells are associated with the pathogenesis of immunodeficiency, systemic autoimmunity and allergy. Despite their importance, we have an incomplete understanding of how TFH cells differentiate and function in distinct inflammatory settings. Answering this question has broad health implications to stimulate rational development of vaccines and therapeutics against diverse infections, autoimmune and allergic disease. In this thesis, I investigated the transcriptional and migration control of TFH differentiation during viral infection. In this setting, TFH cells differentiate in parallel with T helper 1 (TH1) CD4+ T effector cells. I investigated two canonical TH1 factors, T-bet and CXCR3, to understand their roles in TFH cells differentiation. Comparing two viral infections, I demonstrated a context-dependent role for T-bet in TFH differentiation and identified the cytokine and chemokine factors that underlie distinct T cell differentiation. Combined, this work demonstrates that there are multiple paths that direct TFH differentiation. This study has led to further investigations into pathogen-specific TFH programs, which will help us understand how TFH orchestrate tailored B cell responses in diverse infections.
KeywordsT follicular helper cells; Migration; Transcription factors; T-bet; viral infections
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