T Peripheral Helper Cells in Lymphoid Aggregate and Tertiary Lymphoid Structure Formation

Lymphoid aggregates and more mature tertiary lymphoid structures frequently form within chronically inflamed tissues. These structures facilitate local T cell-B cell activation within an inflamed tissue, promoting the ongoing adaptive immune response. Target tissues in autoimmune diseases accumulate a range of CD4 T cells with the capacity to help B cells and promote lymphoid aggregate formation. These B cell-helper T cells include T peripheral helper (Tph) cells, which functionally resemble T follicular helper (Tfh) cells in their capacity to recruit and interact with B cells, yet differ primarily in their migratory capacity. Tph cells accumulate within inflamed tissues such as rheumatoid arthritis synovium, where they serve as a major source of the B cell chemoattractant CXCL13, which can drive recruitment of B cells to a peripheral tissue. Here, we discuss features of Tph cells and other Tfh-like T cell populations that accumulate within chronically inflamed tissues in autoimmune diseases and review the regulation of key factors produced by these cells, including CXCL13 and IL-21. Understanding the range of B cell-helper T cells that accumulate within tissues and the regulation of their differentiation and function may provide new strategies to either inhibit or promote their actions therapeutically.