Cytokines of the TNF/lymphotoxin (LT) family signal the development of organized lymphoid tissues. Mice deficient in LT-a fail to form lymph nodes and Peyer's patches. They also show disturbed spleen white pulp structure, with failure to segregate B cell and T cell zones, and to form primary B cell follicles with clusters of follicular dendritic cells (FDC). TNF also is required for the formation of primary B cell follicles. Infusion of purified LT-expressing B cells restores development of FDC and primary follicle structure. This demonstrates an unexpected role of B cells as organizers of the lymphoid tissue microenvironment in which the B cells themselves ultimately mature. Future studies will define additional signals that establish the normal structure of lymphoid tissues and the functions of this structure on normal and pathological immune responses.
Other studies investigate cytokines as regulators of tissue inflammatory responses, particularly allergic inflammation. These studies have shown that in the skin, IL-1 beta is required for recognition that new antigens have penetrated the epidermis. They have also shown that in the lungs Th1 and Th2 cells cooperate to induce eosinophilic airway inflammation. In the airways, tumor necrosis factor produced by Th1 cells induces VCAM-1 expression that then permits Th2 cell infiltration.
