DEFECTIVE PEYER PATCH ORGANOGENESIS IN MICE LACKING THE 55-KD RECEPTOR FOR TUMOR-NECROSIS-FACTOR

Lymphotoxin alpha (LT-alpha) may from secreted homotrimers binding to p55 and p75 tumor necrosis factor (TNF) receptors or cell surface-boun d heterotrimers with LT-beta that interact with the LT-beta receptor. Genetic ablation of LT-alpha revealed chat mutant mice have no detecta ble lymph nodes or Peyer's patches and that the organization of the sp lenic white pulp in T and B cell areas is disturbed. In this report we describe a novel function for the p55 TNF receptor during ontogeny an d demonstrate that mice deficient for p55 completely lack organized Pe yer's patches. In contrast, lymph nodes and spleen are present in p55- deficient mice and lymphocytes segregate normally into B and T cell ar eas in these organs. Lamina propria and intraepithelial lymphocytes of the small intestine were detected in normal number and distribution i n p55 mutant mice. Lymphocytes and endothelial cells from p55-deficien t mice express normal levels of adhesion molecules considered importan t for lymphocyte migration to mucosal organs; this indicates that the lack of Peyer's patches does not result from a defect in lymphocyte ho ming. In summary, the p55 receptor for TNF selectively mediates organo genesis of Peyer's patches throughout ontogeny, suggesting that tile e ffects of LT-alpha on the development of lymphoid organs may be mediat ed by distinct receptors, each functioning in an organ-specific contex t.