When helper T cells reach peripheral tissues, they interact with various cell types, particularly antigen-presenting cells like macrophages. This interaction involves antigen recognition, costimulation, cytokine production, and feedback regulation. Furthermore, the cytokines produced can significantly impact the immunological microenvironment, recruiting immune cells, modulating resident immune cells, promoting tissue repair, and regulating inflammatory responses.

Helper T cells leaving lymphoid tissues change chemokine receptor expression to migrate to specific inflammatory or infected sites. They downregulate CCR7 and CXCR4 and upregulate CCR5, CXCR3, and CCR6. Different subsets express different receptors, reflecting their functions. For example, Th1 cells express CXCR3 for inflammation, while Th2 cells may express CCR4 for allergic reactions.

When dendritic cells present antigens to naive T cells in lymph nodes, three key signals are involved: antigen recognition (Signal 1), co-stimulatory signal (Signal 2), and T cell polarizing cytokines (Signal 3). These interactions activate, proliferate, and differentiate T cells into specific effector subsets, ensuring tailored immune responses against encountered antigens.