PMID- 32758800 OWN - NLM STAT- MEDLINE DCOM- 20210504 LR - 20210504 IS - 1878-1667 (Electronic) IS - 0147-9571 (Linking) VI - 72 DP - 2020 Oct TI - An engineered anti-idiotypic antibody-derived killer peptide (KP) early activates swine inflammatory monocytes, CD3(+)CD16(+) natural killer T cells and CD4(+)CD8alpha(+) double positive CD8beta(+) cytotoxic T lymphocytes associated with TNF-alpha and IFN-gamma secretion. PG - 101523 LID - S0147-9571(20)30112-0 [pii] LID - 10.1016/j.cimid.2020.101523 [doi] AB - This study evaluated the early modulation of the phenotype and cytokine secretion in swine immune cells treated with an engineered killer peptide (KP) based on an anti-idiotypic antibody functionally mimicking a yeast killer toxin. The influence of KP on specific immunity was investigated using porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) as ex vivo antigens. Peripheral blood mononuclear cells (PBMC) from healthy pigs were stimulated with KP and with a scramble peptide for 20 min, 1, 4 and 20 h or kept unstimulated. The cells were analyzed using flow cytometry and ELISA. The same time-periods were used for KP pre-incubation/co-incubation to determine the effect on virus-recalled interferon-gamma (IFN-gamma) secreting cell (SC) frequencies and single cell IFN-gamma productivity using ELISPOT. KP induced an early dose-dependent shift to pro-inflammatory CD172alpha(+)CD14(+high) monocytes and an increase of CD3(+)CD16(+) natural killer (NK) T cells. KP triggered CD8alpha and CD8beta expression on classical CD4(-)CD8alphabeta(+) cytotoxic T lymphocytes (CTL) and double positive (DP) CD4(+)CD8alpha(+) Th memory cells (CD4(+)CD8alpha(+low) CD8beta(+low)). A fraction of DP cells also expressed high levels of CD8alpha. The two identified DP CD4(+)CD8alpha(+high) CD8beta(+low/+high) CTL subsets were associated with tumor necrosis factor alpha (TNF-alpha) and IFN-gamma secretion. KP markedly boosted the reactivity and cross-reactivity of PRRSV type-1- and PCV2b-specific IFN-gamma SC. The results indicate the efficacy of KP in stimulating Th1-biased immunomodulation and support studies of KP as an immunomodulator or vaccine adjuvant. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Ferrari, Luca AU - Ferrari L AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: luca.ferrari@unipr.it. FAU - Martelli, Paolo AU - Martelli P AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: paolo.martelli@unipr.it. FAU - Saleri, Roberta AU - Saleri R AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: roberta.saleri@unipr.it. FAU - De Angelis, Elena AU - De Angelis E AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: elena.deangelis@unipr.it. FAU - Ferrarini, Giulia AU - Ferrarini G AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: giulia.ferrarini@studenti.unipr.it. FAU - Cavalli, Valeria AU - Cavalli V AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: valeria.cavalli@unipr.it. FAU - Passeri, Benedetta AU - Passeri B AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: benedetta.passeri@unipr.it. FAU - Bazzoli, Gianluca AU - Bazzoli G AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: gianluca.bazzoli@studenti.unipr.it. FAU - Ogno, Giulia AU - Ogno G AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: giulia.ogno@studenti.unipr.it. FAU - Magliani, Walter AU - Magliani W AD - Department of Medicine and Surgery, University of Parma, Via Gramsci, 14 - 43126, Parma, Italy. Electronic address: walter.magliani@unipr.it. FAU - Borghetti, Paolo AU - Borghetti P AD - Department of Veterinary Science, University of Parma, Strada del Taglio, 10 - 43126, Parma, Italy. Electronic address: paolo.borghetti@unipr.it. LA - eng PT - Journal Article DEP - 20200723 PL - England TA - Comp Immunol Microbiol Infect Dis JT - Comparative immunology, microbiology and infectious diseases JID - 7808924 RN - 0 (Antibodies, Anti-Idiotypic) RN - 0 (Peptides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antibodies, Anti-Idiotypic/*immunology MH - Interferon-gamma/*immunology MH - Monocytes/*immunology MH - Natural Killer T-Cells/*immunology MH - Peptides/immunology MH - Swine MH - T-Lymphocytes, Cytotoxic/*immunology MH - Tumor Necrosis Factor-alpha/*metabolism OTO - NOTNLM OT - Cytokines OT - Double positive cytotoxic T lymphocytes (DP CTL) OT - IFN-gamma secreting cells OT - Killer peptide (KP) OT - Natural killer (NK) T cells OT - Porcine circovirus type 2 (PCV2) OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - Pro-inflammatory monocytes OT - TNF-alpha OT - Viral cross-reactivity EDAT- 2020/08/08 06:00 MHDA- 2021/05/05 06:00 CRDT- 2020/08/08 06:00 PHST- 2020/01/10 00:00 [received] PHST- 2020/07/15 00:00 [revised] PHST- 2020/07/19 00:00 [accepted] PHST- 2020/08/08 06:00 [pubmed] PHST- 2021/05/05 06:00 [medline] PHST- 2020/08/08 06:00 [entrez] AID - S0147-9571(20)30112-0 [pii] AID - 10.1016/j.cimid.2020.101523 [doi] PST - ppublish SO - Comp Immunol Microbiol Infect Dis. 2020 Oct;72:101523. doi: 10.1016/j.cimid.2020.101523. Epub 2020 Jul 23.