Peripheral T helper Cells in a Murine Chronic Inflammation Model

Abstract

A germinal center forms in secondary lymphoid organs during a T-cell dependent humoral immune response and yields high-affinity antibodies against incoming pathogens. Within the germinal centers are follicular helper T cells (Tfh) providing help to B cells that are undergoing mutative proliferation. B cells present cognate antigens to Tfh cells, which in turn facilitate B cell differentiation by expressing ligands, such as CD40L and ICOS, and secreting cytokines, including IL-21 and CXCL13. In the context of chronic inflammation and autoimmunity, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), additional T cell populations with similar functional properties to Tfh cells also expand, such as peripheral helper T cells (Tph). Tph cells have not been fully described in mouse yet would provide a valuable tool for assessing their development and effector function. Using a mouse model of lupus induced by pristane, we have discovered a population of T cells that are phenotypically similar to Tph cells identified in humans. Using high-throughput transcriptomic analysis of murine CD4 T cell transcriptomics, we found two B cell helper populations, recapitulating the Tfh and Tph population in pristane treated murine spleens and lungs. Given the functional overlap between Tfh and Tph, we aimed to investigate some of the molecule and cellular factors that are important for Tph development in this model. We observed that Tph development is partially dependent on Bcl6. In the absence of B cells, cells with Tph features decrease in the spleen, but not in the lungs. Altogether, these observations lay the groundwork of mouse models of Tph cells that resemble those in humans, reiterate the differences between Tph and Tfh cells, and allow future research to assess the role of Tph in autoimmune pathology.