Furthermore adult LTi-like cells, just like their counterparts from embryonic day 15 spleen, restore

a significant degree of B/T segregation in the spleen of LTα−/− mice, and up-regulate VCAM-1 and CCL21 protein expression on the stromal cells with which they are associated 6. Most recently, adult LTi-like cells were shown to induce lymphoid tissue formation in the intestine of CXCR5−/− mice 7. Although normal podoplanin (gp38) expression on T-zone stromal cells requires lymphocytes, find more LTi-like cells can provide lymphotoxin signals required for the expression of podoplanin and CCL21 on T-cell zone stroma, as injection of LTα−/− lymphocytes into RAG-deficient mice up-regulates podoplanin on T-zone stroma, and this is associated with B/T segregation and T-cell organization 8. Interactions between LTi-like cells and stromal cells continue into adulthood and are important for restoring SLO integrity and function after virus infection 9. The white pulp of spleen is compartmentalized into B and T zones where cellular and humoral immune responses BKM120 are initiated. In B zones, B cells are intermingled with stromal cells, such as follicular DC 10. T zones contain T cells, DC and fibroblastic reticular cells (FRC) whose relationship to other stromal cells and effects on leukocytes are not fully elucidated 11. FRC ensheath a reticular

network serving as a conduit system for the transport of fluid and soluble substances of low-molecular weight from the blood to the white pulp 12. Soluble Ag and chemokines travel via this conduit system allowing Ag uptake by DC as well as lymphocyte migration within the spleen and other lymphoid tissues 13, 14. FRC express the glycoprotein marker podoplanin but appear to be a heterogeneous cell population, with the most prominent subset forming a dense network throughout the T zone where they produce the extracellular matrix scaffold of the LN 15, 16. Recent findings have

demonstrated that a stromal population of podoplanin+ T-zone reticular cells (TRC) regulates the homeostasis of naïve T cells but not B cells by providing survival factors including IL-7 and CCL19 in LN 17. Collectively, these data suggest that like T-lymphocytes, closely associating with VAV2 stroma, adult LTi-like cells interact with stromal cells to create distinct microenvironments in lymphoid tissues which facilitate effective immune responses. It is therefore important to identify the nature of the stromal cell subsets as well as the molecular pathways involved in LTi survival during the development of the immune system from embryo to adult. In this study, we investigated whether podoplanin+ stromal cells in the adult spleen provide survival signals for adult LTi-like cells. An obvious candidate for LTi survival is cytokine IL-7, whose receptor (IL-7Rα) is expressed on LTi.