title: Phenotypic modulation of porcine CD14+ monocytes, natural killer/natural killer T cells and CD8αβ+ T cell subsets by an antibody-derived killer peptide (KP).
abstract: An engineered killer peptide (KP) based on a recombinant anti-idiotypic antibody representing the functional image of a yeast killer toxin (KT) was demonstrated to mediate antimicrobial effects against fungi and viruses. KP binds to murine dendritic cells and macrophages and up-regulate co-receptor expression, thus sustaining CD4+ lymphocyte activation. No immunological data are available in domestic animals thus KP-induced immunomodulation was evaluated in porcine monocyte and lymphocyte subsets. PBMC from healthy adult pigs were stimulated with KP or a scramble peptide (SP), or kept unstimulated for 24, 48 and 72h, and subsequently analyzed by flow cytometry. In monocytes, KP induced a strong dose-dependent shift from a major fraction of CD172α+CD14+lowcells to a predominant fraction of CD172α+CD14+highcells, known to sustain leukocyte activation/differentiation and inflammatory responses. The CD16+ cell percentages, specifically the CD3+CD16+ natural killer T (NKT) cell fraction and CD16 expression showed an intense and stable dose-dependent increase while the CD3-CD16+ NK cell fraction decreased. CD4+ and CD8+ T cells increased and CD8α and CD8β expression were up-regulated. CD8β+ cytotoxic T cells and CD16+ cells comparably increased. A marked stimulation of activated CD16+CD25+ and CD8β+CD25+ cells was observed at 24h. The increase of CD8α+ cells and CD8α expression were due to increased CD4+CD8α+ (memory T helper) cells, also showing a CD8α+highphenotype. Concomitantly, the CD4+CD8α- T helper lymphocyte fraction significantly decreased. Overall, KP induced a wide modulation of innate immune and T cells that can exert regulatory and cytotoxic functions, which are fundamental for an efficient Th1 response.
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: luca.ferrari@unipr.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Ferrari
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: paolo.borghetti@unipr.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Borghetti
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: giulia.ferrarini@studenti.unipr.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ferrarini
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: elena.deangelis@unipr.it.
authors.forename: Elena
authors.initials: E
authors.lastname: De Angelis
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: elena.canelli@unipr.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Canelli
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: giulia.ogno@studenti.unipr.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ogno
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: alessia.catella@studenti.unipr.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Catella
authors.affiliation: Department of Biomedical, Biotechnological & Translational Sciences (S.Bi.Bi.T), University of Parma, Via Gramsci, 14, Parma 43126, Italy. Electronic address: tecla.ciociola@unipr.it.
authors.forename: Tecla
authors.initials: T
authors.lastname: Ciociola
authors.affiliation: Department of Biomedical, Biotechnological & Translational Sciences (S.Bi.Bi.T), University of Parma, Via Gramsci, 14, Parma 43126, Italy. Electronic address: walter.magliani@unipr.it.
authors.forename: Walter
authors.initials: W
authors.lastname: Magliani
authors.affiliation: Department of Veterinary Science, University of Parma, Via del Taglio, 10, Parma 43126, Italy. Electronic address: paolo.martelli@unipr.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Martelli
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D009000:Monocytes / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D013552:Swine; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000906:Antibodies; D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D018950:Lipopolysaccharide Receptors; D010455:Peptides
keywords: CD172α+CD14+(high) monocytes; CD4+CD8+ cells; Cytotoxic T lymphocytes (CTL); Immunomodulation; Killer peptide (KP); Natural killer (NK)/NKT cells