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Guimond, M. et al. Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells. Nature Immunol. 10, 149–157 (2009).
The first definitive evidence that the increased levels of IL-7 during lymphopaenia are the result of decreased consumption rather than increased production. This study also identifies IL-7-mediated signalling on DCs as a modulator of T cell homeostasis.
ArticlePellegrini, M. et al. Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nature Med. 15, 528–536 (2009).
This study provides mechanistic insight into the vaccine adjuvant effect of IL-7 and increases the known targets of IL-7-mediated signalling to include negative regulators of the T cell response such as CBL-B and SMURF2.
ArticlePark, J. H. et al. Suppression of IL7Rα transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival. Immunity 21, 289–302 (2004).
This study established IL-7 as a limiting resource for T cells.
ArticlePubMedISIChemPortFry, T. J. et al. IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates. Blood 101, 2294–2299 (2003).
The first demonstration that the effects of in vivo IL-7 administration extend to non-human primates. This study also showed that IL-7-mediated signalling downregulates expression of IL-7Rα.
ArticlePubMedChemPortKhaled, A. R. & Durum, S. K. Death and Baxes: mechanisms of lymphotrophic cytokines. Immunol. Rev. 193, 48–57 (2003).
ArticlePubMedISIChemPortJiang, Q. et al. Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev. 16, 513–533 (2005).
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The first description in humans of SCID due to deficiency of IL-7Rα signalling. This study identified important differences in lymphocyte development between mice and humans.
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ArticleMazzucchelli, R. & Durum, S. K. Interleukin-7 receptor expression: intelligent design. Nature Rev. Immunol. 7, 144–154 (2007).
A definitive review of the role of IL-7Rα in T cell development.
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ArticlePubMedISIChemPortKhaled, A. R. et al. Bax deficiency partially corrects interleukin-7 receptor-α deficiency. Immunity 17, 561–573 (2002).
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ArticlePubMedISIChemPortVang, K. B. et al. IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development. J. Immunol. 181, 3285–3290 (2008).
PubMedChemPortMazzucchelli, R. et al. Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP. Blood 112, 3283–3292 (2008).
ArticlePubMedChemPortBayer, A. L., Lee, J. Y., de la Barrera, A., Surh, C. D. & Malek, T. R. A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells. J. Immunol. 181, 225–234 (2008).
PubMedChemPortHerzog, S., Reth, M. & Jumaa, H. Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling. Nature Rev. Immunol. 9, 195–205 (2009).
ArticleParrish, Y. K. et al. IL-7 dependence in human B lymphopoiesis increases during progression of ontogeny from cord blood to bone marrow. J. Immunol. 182, 4255–4266 (2009).
ArticlePubMedChemPortShriner, A. K., Liu, H., Sun, G., Guimond, M. & Alugupalli, K. R. IL-7-dependent B lymphocytes are essential for the anti-polysaccharide response and protective immunity to Streptococcus pneumoniae. J. Immunol. 185, 525–531 (2010).
Kikuchi, K., Lai, A. Y., Hsu, C. L. & Kondo, M. IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF. J. Exp. Med. 201, 1197–1203 (2005).
ArticlePubMedISIChemPortJohnson, K. et al. Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling. Immunity 28, 335–345 (2008).
ArticlePubMedChemPortCorcoran, A. E., Riddell, A., Krooshoop, D. & Venkitaraman, A. R. Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Nature 391, 904–907 (1998).
ArticlePubMedISIChemPortBertolino, E. et al. Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5. Nature Immunol. 6, 836–843 (2005).
ArticleMalin, S. et al. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nature Immunol. 11, 171–179 (2010).
ArticleBrown, V. I. et al. Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signaling. Proc. Natl Acad. Sci. USA 100, 15113–15118 (2003).
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Vosshenrich, C. A. et al. A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nature Immunol. 7, 1217–1224 (2006).
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ArticlePubMedISIChemPortMeier, D. et al. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26, 643–654 (2007).
This study identifies the importance of IL-7 for the homeostasis of LTi cells and, therefore, the ability of IL-7 to regulate SLO development.
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ArticleVonarbourg, C. et al. Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt+ innate lymphocytes. Immunity 33, 736–751 (2010).
ArticlePubMedISIChemPortCella, M., Otero, K. & Colonna, M. Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity. Proc. Natl Acad. Sci. USA 107, 10961–10966 (2010).
ArticlePubMedSchluns, K. S., Kieper, W. C., Jameson, S. C. & Lefrancois, L. Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nature Immunol. 1, 426–432 (2000).
The first demonstration that IL-7 is required for the homeostatic proliferation of CD8+ T cells during lymphopenic conditions.
Takada, K. & Jameson, S. C. Naive T cell homeostasis: from awareness of space to a sense of place. Nature Rev. Immunol. 9, 823–832 (2009).
ArticleOuyang, W., Beckett, O., Flavell, R. A. & Li, M. O. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity 30, 358–371 (2009).
ArticlePubMedChemPortGrenningloh, R. et al. Ets-1 maintains IL-7 receptor expression in peripheral T cells. J. Immunol. 186, 969–976 (2010).
Matsue, H., Bergstresser, P. R. & Takashima, A. Keratinocyte-derived IL-7 serves as a growth factor for dendritic epidermal T cells in mice. J. Immunol. 151, 6012–6019 (1993).
PubMedISIChemPortThang, P. H. et al. The role of IL-1β in reduced IL-7 production by stromal and epithelial cells: a model for impaired T-cell numbers in the gut during HIV-1 infection. J. Intern. Med. 268, 181–193 (2010).
Watanabe, M. et al. Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J. Clin. Invest. 95, 2945–2953 (1995).
ArticlePubMedISIChemPortSawa, Y. et al. Hepatic interleukin-7 expression regulates T cell responses. Immunity 30, 447–457 (2009).
ArticlePubMedChemPortKaech, S. M. et al. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nature Immunol. 4, 1191–1198 (2003).
ArticleTan, J. T. et al. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J. Exp. Med. 195, 1523–1532 (2002).
ArticlePubMedISIChemPortKieper, W. C. et al. Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells. J. Exp. Med. 195, 1533–1539 (2002).
ArticlePubMedISIChemPortDardalhon, V. et al. IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells. Proc. Natl Acad. Sci. USA 98, 9277–9282 (2001).
ArticlePubMedChemPortSwainson, L. et al. IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway. Blood 109, 1034–1042 (2007).
ArticlePubMedISIChemPortErnst, B., Lee, D. S., Chang, J. M., Sprent, J. & Surh, C. D. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11, 173–181 (1999).
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ArticlePubMedISIChemPortPaiardini, M. et al. Loss of CD127 expression defines an expansion of effector CD8+ T cells in HIV-infected individuals. J. Immunol. 174, 2900–2909 (2005).
PubMedISIChemPortSeddiki, N. et al. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203, 1693–1700 (2006).
ArticlePubMedISIChemPortLiu, W. et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ TReg cells. J. Exp. Med. 203, 1701–1711 (2006).
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Bolotin, E., Annett, G., Parkman, R. & Weinberg, K. Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. Bone Marrow Transplant. 23, 783–788 (1999).
The first observation that serum IL-7 levels are increased during lymphopaenia after bone marrow transplantation. These findings were identified as a general feature of lymphopaenia with the discovery of increased IL-7 levels in other clinical conditions associated with T cell deficiency in references 65 and 66.
ArticlePubMedISIChemPortFry, T. J. et al. A potential role for interleukin-7 in T-cell homeostasis. Blood 97, 2983–2990 (2001).
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PubMedISIChemPortStorek, J. et al. Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys. Blood 101, 4209–4218 (2003).
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ArticlePubMedISIChemPortMackall, C. L. et al. IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation. Blood 97, 1491–1497 (2001).
ArticlePubMedISIChemPortMorrissey, P. J. et al. Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation. J. Immunol. 146, 1547–1552 (1991).
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PubMedISIChemPortAndrew, D. & Aspinall, R. IL-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice. J. Immunol. 166, 1524–1530 (2001).
PubMedISIChemPortOkamoto, Y., Douek, D. C., McFarland, R. D. & Koup, R. A. Effects of exogenous interleukin-7 on human thymus function. Blood 99, 2851–2858 (2002).
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ArticlePubMedISIChemPortSeggewiss, R. et al. Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood 110, 441–449 (2007).
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ArticlePubMedChemPortMelchionda, F. et al. Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool. J. Clin. Invest. 115, 1177–1187 (2005).
The first description of the vaccine adjuvant effect of IL-7 and its preferential effects on subdominant antigens.
ArticlePubMedISIChemPortFrankenberger, B. et al. Influence of CD80, interleukin-2, and interleukin-7 expression in human renal cell carcinoma on the expansion, function, and survival of tumor-specific CTLs. Clin. Cancer Res. 11, 1733–1742 (2005).
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