title: Transduction of naive CD4 T cells with kinase-deficient Lck-HIV-Tat fusion protein dampens T cell activation and provokes a switch to regulatory function.
abstract: We show here that T cell differentiation can be altered by exposing naive mouse CD4 T cells to altered T cell receptor signaling, achieved by transducing them with a fusion protein consisting of a modified Lck protein lacking the kinase domain and the HIV-Tat protein transduction domain. The Lck-HIV-Tat fusion protein is internalized into naive mouse T cells within 30 min after application to the medium. Activation of transduced cells in vitro resulted in strongly reduced intracellular calcium mobilization, alterations in cytokine profile, and sustained up-regulation of CD25. The cells had suppressive activity in vitro, but no Foxp3 expression. Our data indicate that signals encountered by a naive T cell during its initial activation can profoundly influence its subsequent functional behavior and elicit T cells, which can have regulatory activity.
authors.affiliation: Division of Molecular Immunology, The National Institute for Medical Research, London, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Veldhoen
authors.forename: Anthony I
authors.initials: AI
authors.lastname: Magee
authors.forename: Mario N
authors.initials: MN
authors.lastname: Penha-Goncalves
authors.forename: Brigitta
authors.initials: B
authors.lastname: Stockinger
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D004247:DNA; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)