Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice.

Abstract

SummaryInterleukin 7 (IL-7) stimulates the proliferation of B cell progenitors, thymocytes, and mature T cells through an interaction with a high affinity receptor (IL-7R) belonging to the hematopoietin receptor superfamily. We have further addressed the role of IL-7 and its receptor during B and T cell development by generating mice genetically deficient in IL-7R. Mutant mice display a profound reduction in thymic and peripheral lymphoid cellularity. Analyses of lymphoid progenitor populations in IL-7R-deficient mice define precisely those developmental stages affected by the mutation and reveal a critical role for IL-7R during early lymphoid development. Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7.

Identification and characterization of Cri1, a locus controlling mortality during Citrobacter rodentium infection in mice

“…It also overlaps the FYNbinding protein (Fyb; 6.5 Mb) for which deficient mice display reduced T-cell proliferation 27 as well as the interleukin 7 receptor (Il7r; 9.4 Mb), known to be an important regulator of B-and T-cell proliferation/ differentiation. 28 Although the Il7r gene seems relatively far proximal of the peak linkage region of the Cri1 locus, it is an intriguing candidate as B-cell function has been found to be essential for C. rodentium infection survival. 19,29,30 Ultimately, however, a continued systematic genetic approach may be required to identify the gene underlying the Cri1 locus.…”

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

“…Interleukin-7 (IL-7) is a non-redundant cytokine, which is required for the generation of new T-cells from the thymus 7 and for the survival of existing T-cells in circulation. 8 IL-7 binds to the dimerized receptors of IL-7 receptor-a (IL-7Ra) (CD127) and the g-chain receptor (CD132) to exert its effect.…”

Selective ablation of the YxxM motif of IL-7Rα suppresses lymphomagenesis but maintains lymphocyte development

“…Similarly, transgenic overexpression of IL-7 (Tg IL-7) caused mixed T-and B-cell lymphomas that arose by oligoclonal expansion of variable subsets, which could form masses upon transfer to either immunocompetent or nude mice (Rich et al, 1993). As IL-7 is essential for both T-and B-cell development in mice and T cells in humans (Peschon et al, 1994;von Freeden-Jeffry et al, 1995;Kovanen and Leonard, 2004), we aimed to determine whether the signals necessary for lymphocyte homeostasis and development could be separated from those required for transformation.…”

“…IL-7Ra has a conserved tyrosine residue, Y449, located in an SH2 domain-binding motif (YXXM), required for the activation of signal transducer and activator of transcription 5 (STAT5) and the phosphoinositide 3 (PI3) kinase/Akt pathway (Pallard et al, 1999;Wofford et al, 2008). In contrast to IL-7Ra knockout mice that are severely lymphopenic because of developmental blocks in both B-and T-cell lineages (Peschon et al, 1994), mice with a targeted Y449 to phenylalanine (F) knock-in mutation at the IL-7Ra locus (IL-7Ra 449F ) show relatively normal T-cell differentiation . As the IL-7Ra 449F mutation allows T-cell differentiation but alters the signaling capacity of the receptor, we tested the hypothesis that IL-7Ra Y449-mediated pathways were essential for lymphoid transformation.…”