An essential role for the IL-7 receptor during intrathymic expansion of the positively selected neonatal T cell repertoire

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.