PMID- 29909133 OWN - NLM STAT- MEDLINE DCOM- 20181016 LR - 20181016 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 36 IP - 30 DP - 2018 Jul 16 TI - Tuberculin skin test reaction is related to memory, but not naive CD4(+) T cell responses to mycobacterial stimuli in BCG-vaccinated young adults. PG - 4566-4577 LID - S0264-410X(18)30708-4 [pii] LID - 10.1016/j.vaccine.2018.05.068 [doi] AB - Bacillus Calmette-Guerin (BCG) is the only vaccine available against tuberculosis and the tuberculin skin test (TST) is the most widely used method to detect BCG take. However, subjects may remain TST-negative, even after several BCG administrations. To investigate some of the potential reasons underlying this inability of developing tuberculin sensitivity in response to BCG we compared the effect of different mycobacterial stimuli in the groups differently responding to tuberculin. TST was performed on 71 healthy adults aged 25-30 years, who had received BCG in their childhood, and considered TST-positive at >/=10 mm. Dendritic cells (DCs) were incubated with PPD, live BCG or rBCGhIL-18, producing human IL-18. The latter strain was used to investigate whether the production of IL-18 could overcome some of the immune read-out limitations in the TST-negative subjects. CD86, CD80, CD40, and DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression was analysed by flow cytometry and IL-10, IL-23 and IP-10 secretion in culture supernatants by ELISA. In DCs-T cell co-cultures with naive and memory CD4(+) T cells, the IFN-gamma and IL-10 levels were determined by ELISA. We found no difference in IL-10 and IFN-gamma production by naive T cells between the TST-negative and TST-positive subjects. However, IFN-gamma was produced in significantly higher amounts by memory T cells incubated with PPD, BCG or rBCGhIL-18-pulsed DCs in TST-positive than in TST-negative subjects, whereas the numbers of the IFN-gamma-producing T cells were similar in both groups. This difference may be partially due to a decreased CD40 and enhanced reduction in DC-SIGN expression by DCs of TST-negative versus TST-positive subjects. A strong effect of IL-18 expression by rBCGhIL-18 on IL-23 production by the DC was seen in both groups, which likely was the reason for the increased IFN-gamma production by naive T cells upon incubation with mycobacteria-pulsed DC, regardless of the TST status. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Kowalewicz-Kulbat, Magdalena AU - Kowalewicz-Kulbat M AD - Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. Electronic address: magdalena.kowalewicz@biol.uni.lodz.pl. FAU - Szpakowski, Piotr AU - Szpakowski P AD - Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland; Department of Neurology and Stroke, Medical University of Lodz, Lodz, Poland. FAU - Locht, Camille AU - Locht C AD - Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France; Inserm U1019, Lille, France; CNRS UMR 8204, Lille, France; Universite Lille Nord de France, Lille, France. FAU - Biet, Franck AU - Biet F AD - UMR1282 Infectiologie et Sante Publique (ISP-311), INRA Centre Val de Loire, Nouzilly, France. FAU - Kaplonek, Paulina AU - Kaplonek P AD - Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. FAU - Krawczyk, Krzysztof T AU - Krawczyk KT AD - Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. FAU - Pestel, Joel AU - Pestel J AD - Universite Lille Nord de France, Lille, France; CNRS-UMR 8576, Unite de Glycobiologie Structurale et Fonctionnelle, IFR 147, Universite Lille Nord de France, Universite de Lille 1, Villeneuve d'Ascq, France. FAU - Rudnicka, Wieslawa AU - Rudnicka W AD - Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180619 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (BCG Vaccine) SB - IM MH - Adult MH - BCG Vaccine/immunology MH - CD4-Positive T-Lymphocytes MH - Dendritic Cells/immunology MH - Female MH - Humans MH - Male MH - Monocytes/immunology MH - T-Lymphocyte Subsets/immunology MH - Tuberculin Test/*methods MH - Young Adult OTO - NOTNLM OT - BCG OT - Cytokines OT - Dendritic cells (DCs) OT - T cells OT - Tuberculin skin test (TST) OT - rBCGhIL-18 EDAT- 2018/06/18 06:00 MHDA- 2018/10/17 06:00 CRDT- 2018/06/18 06:00 PHST- 2018/01/23 00:00 [received] PHST- 2018/05/11 00:00 [revised] PHST- 2018/05/13 00:00 [accepted] PHST- 2018/06/18 06:00 [pubmed] PHST- 2018/10/17 06:00 [medline] PHST- 2018/06/18 06:00 [entrez] AID - S0264-410X(18)30708-4 [pii] AID - 10.1016/j.vaccine.2018.05.068 [doi] PST - ppublish SO - Vaccine. 2018 Jul 16;36(30):4566-4577. doi: 10.1016/j.vaccine.2018.05.068. Epub 2018 Jun 19.