Cytokine/stromal cell networks and lymphoid tissue environments.

Initiation of an effective adaptive immune response against a foreign pathogen requires orchestrated encounters between lymphocytes and antigen-presenting cells. The tissues of the lymphoid system provide the ideal environment for increasing the efficiency of these encounters. Within the spleen, the mucosal-associated lymphoid tissues, and the lymph nodes, an intricate network of stromal cells, collagen fibers, and extracellular matrix exists that effectively compartmentalizes immune cells as they transit through these tissues. The stromal cells within lymphoid tissues are by no means homogenous, and it is now clear that these cells are not merely sessile bystanders during immune responses. Indeed, stromal cells within lymphoid tissues are the source of important cytokines and chemokines that guide and polarize immune cells. Here, we review the cytokines that maintain the integrity of this important stromal scaffold system within the lymphoid tissue, paying particular attention to the Lymphotoxin pathway, which is an important player in stromal cell biology. How cytokines maintain the organization of lymphoid tissues during development, in the adult animal, during inflammation and during disease will be discussed in sequence, and the clinical implications of targeting cytokines that regulate lymphoid tissue stroma will be considered.