title: Kruppel-like factor 2 is required for trafficking but not quiescence in postactivated T cells.
abstract: The transcription factor Kruppel-like factor 2 (KLF2) was proposed to regulate genes involved in cell cycle entry and T cell trafficking; however, the physiological role of its expression in postactivated T cells is not well defined. Previous studies suggested that the cytokines IL-2 and IL-15 differentially regulate KLF2 re-expression in postactivation T cells and that these cytokines also influence effector versus memory T cell differentiation. Using conditional and inducible KLF2-knockout model systems, we tested the specific role of KLF2 expression in activated CD8(+) T cells cultured with these cytokines. KLF2 was required for effective transcription of sphingosine-1-phosphate receptor-1 (S1P(1)) and CD62L in postactivation T cells. However, although different cytokines dramatically altered the expression of cell-cycle-related genes, endogenous KLF2 had a minimal impact. Correspondingly, KLF2-deficient T cells showed dysregulated trafficking but not altered proliferative characteristics following in vivo responses to Ag. Thus, our data help to define KLF2-dependent and -independent aspects of activated CD8(+) T cell differentiation and argue against a physiological role in cell cycle regulation.
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55414, USA. takada@genome.tokushima-u.ac.jp
authors.forename: Kensuke
authors.initials: K
authors.lastname: Takada
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Hart
authors.forename: Oludare A
authors.initials: OA
authors.lastname: Odumade
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weinreich
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D019041:L-Selectin / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D013997:Time Factors
chemical_list: D000941:Antigens; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C491561:Sip1 protein, mouse; D019041:L-Selectin; D010047:Ovalbumin