title: Distinct IL-7 signaling in recent thymic emigrants versus mature naïve T cells controls T-cell homeostasis.
abstract: IL-7 is essential for T-cell survival but its availability is limited in vivo. Consequently, all peripheral T cells, including recent thymic emigrants (RTEs) are constantly competing for IL-7 to survive. RTEs are required to replenish TCR diversity and rejuvenate the peripheral T-cell pool. However, it remains unknown how RTEs successfully compete with resident mature T cells for IL-7. Moreover, RTEs express low levels of IL-7 receptors, presumably rendering them even less competitive. Here, we show that, surprisingly, RTEs are more responsive to IL-7 than mature naïve T cells as demonstrated by markedly increased STAT5 phosphorylation upon IL-7 stimulation. Nonetheless, adoptive transfer of RTE cells into lymphopenic host mice resulted in slower IL-7-induced homeostatic proliferation and diminished expansion compared to naïve donor T cells. Mechanistically, we found that IL-7 signaling in RTEs preferentially upregulated expression of Bcl-2, which is anti-apoptotic but also anti-proliferative. In contrast, naïve T cells showed diminished Bcl-2 induction but greater proliferative response to IL-7. Collectively, these data indicate that IL-7 responsiveness in RTE is designed to maximize survival at the expense of reduced proliferation, consistent with RTE serving as a subpopulation of T cells rich in diversity but not in frequency.
authors.affiliation: Experimental Transplantation and Immunology Branch, Bethesda, MD, USA.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Waickman
authors.affiliation: Experimental Transplantation and Immunology Branch, Bethesda, MD, USA.
authors.forename: Ehydel
authors.initials: E
authors.lastname: Castro
authors.affiliation: Experimental Transplantation and Immunology Branch, Bethesda, MD, USA.
authors.forename: Francis A
authors.initials: FA
authors.lastname: Flomerfelt
authors.affiliation: Experimental Transplantation and Immunology Branch, Bethesda, MD, USA.
authors.forename: Nga V
authors.initials: NV
authors.lastname: Hawk
authors.affiliation: Experimental Transplantation and Immunology Branch, Bethesda, MD, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Kapoor
authors.affiliation: Experimental Transplantation and Immunology Branch, Bethesda, MD, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Telford
authors.affiliation: Experimental Transplantation and Immunology Branch, Bethesda, MD, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency; D006706:Homeostasis; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; C499308:Rag2 protein, mouse; D020395:Receptors, Interleukin-7
keywords: Apoptosis ⋅ Bcl-2 ⋅ Cytokine ⋅ Proliferation ⋅ STAT5