Role of Lymphotoxin and TNF in the devel. of lymphoid

Basic Sciences

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Abstract

In the reported period we further dissected the role of LT and TNF in the development of Peyer's patches (PP). Our conditional knockout models have been generated in collaboration with L. Tessarollo and C. Steart. Firstly, in collaboration with A. Chervonsky from the Jackson Lab and D. Kuprash from the Engelhardt Institute, Moscow, we have demonstrated that LT and TNF produced by B cells are required for development of lymphoid follicles in PP, but are dispensable for maintenance of the follicle-associated epithelium. Secondly, we generated novel neo-free TNF KO mice which completely lack PP. This allowed us, in collaboration with W. Murphy from University of Nevada and D. Kuprash from the Engelhardt Institute, Moscow, to readdress the role of PP in GVHD. Our study indicates that neither TNF, nor the presence of PP, are required for GVHD in protocols with extensive conditioning of the host. Finally, our experiments with the panel of cell-type specific LT and TNF knockouts have established organ-specific "rules" for the role of these cytokines in organization of spleen, lymph nodes and Peyer's patches.