title: TGF-β sensitivity restrains CD8+ T cell homeostatic proliferation by enforcing sensitivity to IL-7 and IL-15.
abstract: The pleiotropic cytokine TGF-β has been implicated in the regulation of numerous aspects of the immune response, including naïve T cell homeostasis. Previous studies found that impairing TGF-β responsiveness (through expression of a dominant-negative TGF-β RII [DNRII] transgene) leads to accumulation of memory phenotype CD8 T cells, and it was proposed that this resulted from enhanced IL-15 sensitivity. Here we show naïve DNRII CD8 T cells exhibit enhanced lymphopenia-driven proliferation and generation of "homeostatic" memory cells. However, this enhanced response occurred in the absence of IL-15 and, unexpectedly, even in the combined absence of IL-7 and IL-15, which were thought essential for CD8 T cell homeostatic expansion. DNRII transgenic CD8 T cells still require access to self Class I MHC for homeostatic proliferation, arguing against generalized dysregulation of homeostatic cues. These findings suggest TGF-β responsiveness is critical for enforcing sensitivity to homeostatic cytokines that limit maintenance and composition of the CD8 T cell pool. (154 words).
authors.affiliation: Lab Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Lisa D S
authors.initials: LD
authors.lastname: Johnson
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D049109:Cell Proliferation; D005799:Genes, Dominant / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006706:Homeostasis; D019409:Interleukin-15 / Q000378:metabolism*; D015851:Interleukin-7 / Q000378:metabolism*; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D015851:Interleukin-7; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II