Mice deficient in lymphotoxin alpha (LT-a -/-) have a phenotype characterized by lack of morphologically detectable secondary lymphoid tissue. Specifically- LTa -/- mice lack lymph nodes, Peyer's patches, and their spleens show abnormal organization of the white pulp (1,2,3). Preliminary work indicates that the thymus, as well as thymic and bone marrow development of T and B cell populations, are normal. Immunologically, limited studies indicate inpaired but not absent immune responses. The characterization studies of the LTa -/- mice developed in our laboratory are under review and the manuscript describing such studies is included as an appendix. The most interesting aspect of the LTa -/- mouse is the observation that secondary lymphoid organogenesis is profoundly changed. This should provide a model not only to better understand lymph node development, but also a system to evaluate the role of secondary lymphoid organs for immune induction. The efforts of my investigation will be to a) attempt to further define cellular and molecular events involved in secondary lymphoid development and b) assess the mucosal immunological implications of the absence of Peyer's patches. The initial emphasis will be on the immunological investigations.
