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During evolution, GALT develops from primitive lymphoid cell clusters with bothhematopoietic and immune function to organized tissues able to generate highly specific adaptive immune responses. In mice, the cellular interactions between lymphoid tissue inducer cells and mesenchymal organizer cells regulate PP and LN development during ontogeny. The formation of cell clusters triggers a series of signaling events involving adhesion molecules, cytokines, chemokines, and TNF-family member molecules. The activation of integrins via molecular feedback loops appears to be essential for the prolonged cell-to-cell contact between the inducer and the organizer cells. The expression of adhesion molecules and chemokines by organizer cells is induced via LTPR signaling, thus leading to the recruitment and compartmentalization of mature lymphocyte subsets. The inducer cells are the major cell population engaging LTpR on stromal cells via LTap. After birth, the maintenance of organized lymphoid tissue is still dependent on signaling via TNF-family receptors, and other lymphoid cells such as B cells and T cells as well as microbial stimuli may trigger lymphoid tissue organization. It is evident that different TNF family member molecules, cytokines, and chemokines have a synergistic function in lympho-organogenesis, and the availability of these factors determines the formation of PPs, mucosa-draining LNs, or peripheral LNs. Similar mechanisms may operate during the neoformation of lymphoid tissue at sites of chronic inflammation.

Acknowledgements We sincerely apologize to all the colleagues whose work has been omitted because of space limitations. We wish to thank Dr. R. Ceredig and the members of the Developmental Immunology Division for critical reading of the manuscript and L. Du Pasquier for discussions and insights into the phylogenetic development of the immune system. DF is supported by grants from the Swiss National Science Foundation, the Walter Honegger Foundation and the Swiss Cancer League. D. Meier is supported by the Wehrenfels Foundation.

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How To Bolster Your Immune System

How To Bolster Your Immune System

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