Successful development of methodology for detection of hapten-specific contact hypersensitivity (CHS) memory in swine

Autoři: E. J. Putz aff001;  A. M. Putz aff001;  A. Boettcher aff001;  S. Charley aff001;  M. Sauer aff001;  M. Palmer aff003;  R. Phillips aff002;  J. Hostetter aff002;  C. L. Loving aff004;  J. E. Cunnick aff001;  C. K. Tuggle aff001
Působiště autorů: Iowa State University, Department of Animal Science, Ames, IA, United States of America aff001;  Iowa State University College of Veterinary Medicine, Department of Veterinary Pathology Science, Ames, IA, United States of America aff002;  USDA-ARS-National Animal Disease Center, Infectious Bacterial Diseases of Livestock Research Unit, Ames, IA, United States of America aff003;  USDA-ARS-National Animal Disease Center, Food Safety and Enteric Pathogens Research Unit, Ames, IA, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Hapten contact hypersensitivity (CHS) elicits a well-documented inflammation response that can be used to illustrate training of immune cells through hapten-specific CHS memory. The education of hapten-specific memory T cells has been well-established, recent research in mice has expanded the “adaptive” characteristic of a memory response from solely a function of the adaptive immune system, to innate cells as well. To test whether similar responses are seen in a non-rodent model, we used hapten-specific CHS to measure the ear inflammation response of outbred pigs to dinitrofluorobenzene (DNFB), oxazolone (OXA), or vehicle controls. We adapted mouse innate memory literature protocols to the domestic pig model. Animals were challenged up to 32 days post initial sensitization exposure to the hapten, and specific ear swelling responses to this challenge were significant for 7, 21, and 32 days post-sensitization. We established hapten-specific CHS memory exists in a non-rodent model. We also developed a successful protocol for demonstrating these CHS responses in a porcine system.

Klíčová slova:

Ears – Inflammation – Necrosis – Pig models – Swine – Haptens – Intradermal injections – NK cells


1. Askenase PW. Yes T cells, but three different T cells (alphabeta, gammadelta and NK T cells), and also B-1 cells mediate contact sensitivity. Clinical and experimental immunology. 2001;125(3):345–50. Epub 2001/09/05. doi: 10.1046/j.1365-2249.2001.01619.x 11531940; PubMed Central PMCID: PMC1906150.

2. Majewska-Szczepanik M, Paust S, von Andrian UH, Askenase PW, Szczepanik M. Natural killer cell-mediated contact sensitivity develops rapidly and depends on interferon-alpha, interferon-gamma and interleukin-12. Immunology. 2013;140(1):98–110. Epub 2013/05/11. doi: 10.1111/imm.12120 23659714; PubMed Central PMCID: PMC3809710.

3. Majewska-Szczepanik M, Zemelka-Wiacek M, Ptak W, Wen L, Szczepanik M. Epicutaneous immunization with DNP-BSA induces CD4+ CD25+ Treg cells that inhibit Tc1-mediated CS. Immunology and cell biology. 2012;90(8):784–95. Epub 2012/02/01. doi: 10.1038/icb.2012.1 22290507.

4. Szczepanik M, Anderson LR, Ushio H, Ptak W, Owen MJ, Hayday AC, et al. Gamma delta T cells from tolerized alpha beta T cell receptor (TCR)-deficient mice inhibit contact sensitivity-effector T cells in vivo, and their interferon-gamma production in vitro. The Journal of experimental medicine. 1996;184(6):2129–39. Epub 1996/12/01. doi: 10.1084/jem.184.6.2129 8976169; PubMed Central PMCID: PMC2196372.

5. Kimber I, Dearman RJ. Allergic contact dermatitis: the cellular effectors. Contact dermatitis. 2002;46(1):1–5. Epub 2002/03/29. doi: 10.1034/j.1600-0536.2002.460101.x 11918579.

6. Erkes DA, Selvan SR. Hapten-induced contact hypersensitivity, autoimmune reactions, and tumor regression: plausibility of mediating antitumor immunity. Journal of immunology research. 2014;2014:175265. Epub 2014/06/21. doi: 10.1155/2014/175265 24949488; PubMed Central PMCID: PMC4052058.

7. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science (New York, NY). 2011;331(6013):44–9. Epub 2011/01/08. doi: 10.1126/science.1198687 21212348; PubMed Central PMCID: PMC3089969.

8. Ifrim DC, Quintin J, Joosten LA, Jacobs C, Jansen T, Jacobs L, et al. Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clinical and vaccine immunology: CVI. 2014;21(4):534–45. Epub 2014/02/14. doi: 10.1128/CVI.00688-13 24521784; PubMed Central PMCID: PMC3993125.

9. O'Leary JG, Goodarzi M, Drayton DL, von Andrian UH. T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nature immunology. 2006;7(5):507–16. Epub 2006/04/18. doi: 10.1038/ni1332 16617337.

10. Paust S, Gill HS, Wang BZ, Flynn MP, Moseman EA, Senman B, et al. Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses. Nature immunology. 2010;11(12):1127–35. Epub 2010/10/26. doi: 10.1038/ni.1953 20972432; PubMed Central PMCID: PMC2982944.

11. O'Sullivan TE, Sun JC, Lanier LL. Natural Killer Cell Memory. Immunity. 2015;43(4):634–45. Epub 2015/10/22. doi: 10.1016/j.immuni.2015.09.013 26488815; PubMed Central PMCID: PMC4621966.

12. Paust S, von Andrian UH. Natural killer cell memory. Nature immunology. 2011;12(6):500–8. Epub 2011/07/09. 21739673.

13. Nuhaily S, Damaj BB, Maghazachi AA. Oxazolone-induced delayed type hypersensitivity reaction in the adult yucatan pigs. A useful model for drug development and validation. Toxins. 2009;1(1):25–36. Epub 2009/09/01. doi: 10.3390/toxins1010025 22069530; PubMed Central PMCID: PMC3202774.

14. Vana G, Meingassner JG. Morphologic and immunohistochemical features of experimentally induced allergic contact dermatitis in Gottingen minipigs. Veterinary pathology. 2000;37(6):565–80. Epub 2000/12/06. doi: 10.1354/vp.37-6-565 11105946.

15. Dawson HD, Loveland JE, Pascal G, Gilbert JG, Uenishi H, Mann KM, et al. Structural and functional annotation of the porcine immunome. BMC genomics. 2013;14:332. Epub 2013/05/17. doi: 10.1186/1471-2164-14-332 23676093; PubMed Central PMCID: PMC3658956.

16. Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V. The pig: a model for human infectious diseases. Trends in microbiology. 2012;20(1):50–7. Epub 2011/12/14. doi: 10.1016/j.tim.2011.11.002 22153753.

17. Rajao DS, Loving CL, Waide EH, Gauger PC, Dekkers JC, Tuggle CK, et al. Pigs with Severe Combined Immunodeficiency Are Impaired in Controlling Influenza A Virus Infection. Journal of innate immunity. 2017;9(2):193–202. Epub 2016/12/19. doi: 10.1159/000451007 27988511; PubMed Central PMCID: PMC5330784.

18. R Core Team. R: A language and environment for statistical computing Vienna, Austria: R Foundation for Statistical Computing; 2016. Available from:

19. Lenth RV. Least-squares means: the R package lsmeans. Journal of Statistical Software. 2016;69(1):1–33. doi: 10.18637/jss.v069.i01

20. Powell EJ, Cunnick JE, Tuggle CK. SCID pigs: An emerging large animal NK model. Journal of rare diseases research & treatment. 2017;2(3):1–6. Epub 2017/11/21. 29152615; PubMed Central PMCID: PMC5690567.

21. Powell EJ, Charley S, Boettcher AN, Varley L, Brown J, Schroyen M, et al. Creating effective biocontainment facilities and maintenance protocols for raising specific pathogen-free, severe combined immunodeficient (SCID) pigs. Laboratory animals. 2018;52(4):402–12. Epub 2018/01/13. doi: 10.1177/0023677217750691 29325489.

22. Lee K, Kwon DN, Ezashi T, Choi YJ, Park C, Ericsson AC, et al. Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(20):7260–5. Epub 2014/05/07. doi: 10.1073/pnas.1406376111 24799706; PubMed Central PMCID: PMC4034252.

Článek vyšel v časopise


2019 Číslo 10
Nejčtenější tento týden