Organogenesis of lymph nodes and Peyer’s patches is initiated during embryonic development and depends on the correct expression of a wide variety of molecules. Essential for this process is the paracrine triggering of stromal cells by CD45⁺CD4⁺CD3⁻ cells. Hereto CD45⁺CD4⁺CD3⁻ cells and stromal cells need to be spatially positioned in close proximity to each other. Expression of adhesion molecules and chemokines is thought to be essential for this process. During adult life, similar processes might also be at the basis of development of organized tertiary lymphoid structures often seen in inflammatory lesions.