Essential role of lymph nodes in contact hypersensitivity revealed in lymphotoxin-alpha-deficient mice

Lymph nodes (LNs) are important sentinal organs, populated by circulating l ymphocytes and antigen-bearing cells exiting the tissue beds. Although cell ular and humoral immune responses are induced in LNs by antigenic challenge , it is not known if LNs an essential for acquired immunity. We examined im mune responses in mice that lack LNs due to genetic deletion of lymphotoxin ligands or in utero blockade of membrane lymphotoxin. We report that LNs a re absolutely required for generating contact hypersensitivity, a T cell-de pendent cellular immune response induced by epicutaneous hapten. We show th at the homing of epidermal Langerhans cells in response to hapten applicati on is specifically directed to LNs, providing a cellular basis for this uni que LN function. In contrast, the spleen cannot mediate contact hypersensit ivity because antigen-bearing epidermal Langerhans cells do not access sple nic white pulp. Finally, we formally demonstrate that LNs provide a unique environment essential for generating this acquired immune response by revel -sing the LN defect in lymphotoxin-alpha (-/-) mice, thereby restoring the capacity for contact hypersensitivity.