Cover Picture: The cover image features a frozen section from an embryonic day 16 mouse spleen stained by immunofluorescence to demonstrate the presence and location of lymphoid tissue inducer (LTi) cells. Withers et al. (pp. 3240–3245) show that these cells form the focus of lymphocyte accumulation in the developing mouse spleen. Red staining for CD45 marks haemopoietic cells, green shows

Abstract

AbstractCD4+CD3– lymphoid tissue inducer (LTi) cells are crucial for the development and organisation of lymph nodes and gut associated lymphoid tissues. In this report, we characterise their appearance in the developing spleen and highlight their importance in relation to the development of splenic T cell zones. LTi cells were detected in embryonic spleen from embryonic day 13, although their progenitors were present at embryonic day 12. These cells clustered initially around splenic blood vessels in a lymphotoxin (LT)‐independent manner, but up‐regulation of VCAM‐1 expression on stromal cells associated with the blood vessels was LT dependent. After birth, T cell colonisation of these clusters to form nascent white pulp areas was also LT dependent. Transfer experiments reconstituting RAG–/– mice with either WT or LTα–/– splenocytes demonstrated that lymphocyte expression of LT was not essential for the organisation of a discrete CD3+ T cell zone with localised podoplanin and CCL21 expression. Our studies indicate that a combination of LT signals from LTi cells and LT‐independent signals from lymphocytes is sufficient for expression of podoplanin and CCL21 on splenic T cell zone stroma and subsequent T cell organisation.