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The Journal of Immunology, 00, 165: 2410-2414.
Copyright © 00 by The American Association of Immunologists

An Essential Role for the IL-7 Receptor During Intrathymic Expansion of the Positively Selected Neonatal T Cell Repertoire1

Katherine J. Hare, Eric J. Jenkinson and Graham Anderson2

Department of Anatomy, Division of Immunity and Infection, Medical School, University of Birmingham, B15 2TT, Birmingham, United Kingdom

Intrathymic T cell development is a multistage process involving discrete phases of proliferation as well as differentiation. From studies on IL-7 or IL-7R{alpha}-deficient mice, it is clear that the IL-7 receptor (IL-7R) plays a critical role during the initial stages of intrathymic CD4-8- precursor development. In contrast, the role of IL-7R in later stages of thymocyte development are unclear. Here, we have used various approaches to investigate directly the role of the IL-7R in thymocyte positive selection and the recently described phase of postselection proliferation. First, we show that positive selection involves selective up-regulation of IL-7R{alpha}- and IL-7R{gamma}-chains, with the majority of CD4+ and CD8+ cells being IL-7R+. Second, MHC class II+ thymic epithelium—which drives postselection proliferation—expresses IL-7 mRNA. Finally, analysis of positive selection and postselection proliferation in thymocytes from IL-7R{alpha}-/- neonates shows that positive selection occurs normally, whereas postselection expansion is drastically reduced. Thus, our data provide the first evidence that, as well as playing a role during early phases of thymic development, IL-7R mediates intrathymic expansion of positively selected thymocytes, which may aid in establishment of the neonatal peripheral T cell pool.




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