PMID- 29326720 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 8 DP - 2017 TI - Improved Cytotoxic T Lymphocyte Responses to Vaccination with Porcine Reproductive and Respiratory Syndrome Virus in 4-1BB Transgenic Pigs. PG - 1846 LID - 10.3389/fimmu.2017.01846 [doi] LID - 1846 AB - Vaccination is the most reliable measure to prevent infectious diseases in domestic animals. Development of novel vaccines demands extensive studies with new technologies, such as using novel adjuvants and immunomodulatory molecules. The co-stimulatory molecule 4-1BB provides a key signal that directs the fate of T cells during activation, and thus is important to their function in immune protection. To determine whether host immune responses to viral infection could be promoted by enhancing 4-1BB co-stimulation, in this study, we produced transgenic pig clones expressing an extra copy of the 4-1BB gene by clustered regularly interspaced short palindromic repeats/CRISPR-associated gene 9-mediated homologous recombination at the Rosa26 locus. The immune responses of transgenic pigs to porcine reproductive and respiratory syndrome virus (PRRSV) vaccine were determined on day 14. We show that peripheral blood lymphocytes of transgenic pigs expressed around twice the level of 4-1BB mRNA than those of control pigs. We also found IL-2, TNF-alpha, and granzyme B mRNA levels as well as PRRSV-specific IFN-gamma response were significantly upregulated in 4-1BB transgenic pigs, leading to more efficient cytotoxic T lymphocyte (CTL) killing, whereas the expressions of IL-4, IL-17, and Foxp3 were not affected. These results indicate that higher levels of 4-1BB expression involve in promoting Th1 differentiation and enhancing specific CTL responses to PRRSV, and provide a novel approach to increase the efficacy of current vaccines to control the infectious diseases. FAU - Huang, Guangping AU - Huang G AD - State Key Laboratory for Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China. AD - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China. FAU - Liu, Xianyong AU - Liu X AD - State Key Laboratory for Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China. AD - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China. FAU - Duszynski, Donal W AU - Duszynski DW AD - Department of Biology, University of New Mexico, Albuquerque, NM, United States. FAU - Tang, Xiaoli AU - Tang X AD - State Key Laboratory for Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China. AD - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China. FAU - El-Ashram, Saeed AU - El-Ashram S AD - State Key Laboratory for Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China. AD - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China. FAU - Liu, Zhengzhu AU - Liu Z AD - Department of Animal Science and Veterinary Medicine, Hebei Normal University of Science and Technology, Qinhuangdao, Hebei, China. FAU - Suo, Xun AU - Suo X AD - State Key Laboratory for Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China. AD - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China. FAU - Li, Qiuyan AU - Li Q AD - State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China. LA - eng PT - Journal Article DEP - 20171218 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC5741594 OTO - NOTNLM OT - 4-1BB OT - co-stimulation OT - immune response OT - transgenic pig OT - viral infection EDAT- 2018/01/13 06:00 MHDA- 2018/01/13 06:01 PMCR- 2017/01/01 CRDT- 2018/01/13 06:00 PHST- 2017/06/09 00:00 [received] PHST- 2017/12/06 00:00 [accepted] PHST- 2018/01/13 06:00 [entrez] PHST- 2018/01/13 06:00 [pubmed] PHST- 2018/01/13 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2017.01846 [doi] PST - epublish SO - Front Immunol. 2017 Dec 18;8:1846. doi: 10.3389/fimmu.2017.01846. eCollection 2017.