Analysis Of Regulatory T Cells With An Interferon Gene Signature During Influenza Infection

Abstract

Regulatory T cells are antigen-specific immune suppressors that can be found in circulation or residing in tissues or secondary lymphoid organs. In an effort to characterize Tregs that arise in response to influenza and are found in the lung, the Farrar lab recently performed single-cell RNA sequencing on murine Tregs isolated at various time points throughout infection from the lung. We hypothesized that different subsets of lung Tregs induced by influenza would play unique roles in either suppressing immunity or in resolving inflammation. As part of this thesis, I have carried out an independent analysis of this dataset investigating both the diversity and kinetics of Tregs over the course of infection. Utilizing a series of mouse models to selectively deplete either all Tregs or specific Treg subsets at various times, my data suggests that depletion of Tregs starting at day 6 post infection may lead to the expansion of influenza-specific IgA+ antibody secreting cells in the lungs. I attempted to determine the contribution of Type 1 interferon stimulated Tregs to the influenza immune response. However, my results ultimately demonstrated that the existing Mx1-Cre transgenic mouse line exhibits variegated expression of Cre-recombinase, and thus cannot be used to accurately mark and deplete all ISG-Tregs. These results give insight into the trafficking of specific Treg subsets during flu infection, and highlight technical hurdles to be overcome if we wish to continue to study Type 1 interferon stimulated Tregs.