Progress on chicken T cell immunity to viruses

  • Manman Dai
  • Chenggang Xu
  • Weisan ChenEmail author
  • Ming LiaoEmail author


Avian virus infection remains one of the most important threats to the poultry industry. Pathogens such as avian influenza virus (AIV), avian infectious bronchitis virus (IBV), and infectious bursal disease virus (IBDV) are normally controlled by antibodies specific for surface proteins and cellular immune responses. However, standard vaccines aimed at inducing neutralizing antibodies must be administered annually and can be rendered ineffective because immune-selective pressure results in the continuous mutation of viral surface proteins of different strains circulating from year to year. Chicken T cells have been shown to play a crucial role in fighting virus infection, offering lasting and cross-strain protection, and offer the potential for developing universal vaccines. This review provides an overview of our current knowledge of chicken T cell immunity to viruses. More importantly, we point out the limitations and barriers of current research and a potential direction for future studies.


Chicken CD8+ T cell response CD4+ T cell response Virus Epitope 


Author contributions

MMD drafted the manuscript. WSC, ML, and CGX revised the manuscript.


This work was supported by the National Natural Science Foundation Grants (31802174 and 31830097) and a China Postdoctoral Science Foundation Grant (2018M630956).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of financial interest.


  1. 1.
    Xu C, Ye H, Qiu W, Lin H, Chen Y, Zhang H, Liao M (2018) Phylogenetic classification of hemagglutinin gene of H9N2 avian influenza viruses isolated in China during 2012–2016 and evaluation of selected candidate vaccine strains. Poult Sci 97:3023–3030CrossRefGoogle Scholar
  2. 2.
    Yang HM, Zhao J, Xue J, Yang YL, Zhang GZ (2017) Antigenic variation of LaSota and genotype VII Newcastle disease virus (NDV) and their efficacy against challenge with velogenic NDV. Vaccine 35:27–32CrossRefGoogle Scholar
  3. 3.
    Feng K, Wang F, Xue Y, Zhou Q, Chen F, Bi Y, Xie Q (2017) Epidemiology and characterization of avian infectious bronchitis virus strains circulating in southern China during the period from 2013–2015. Sci Rep 7:6576CrossRefGoogle Scholar
  4. 4.
    Li K, Courtillon C, Guionie O, Allee C, Amelot M, Qi X, Gao Y, Wang X, Eterradossi N (2015) Genetic, antigenic and pathogenic characterization of four infectious bursal disease virus isolates from China suggests continued evolution of very virulent viruses. Infect Genet Evol J Mol Epidemiol Evolut Genet Infect Dis 30:120–127Google Scholar
  5. 5.
    McKinstry KK, Dutton RW, Swain SL, Strutt TM (2013) Memory CD4 T cell-mediated immunity against influenza A virus: more than a little helpful. Arch Immunol Ther Exp 61:341–353CrossRefGoogle Scholar
  6. 6.
    Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515–548CrossRefGoogle Scholar
  7. 7.
    Bernard D, Hansen JD, Du Pasquier L, Lefranc MP, Benmansour A, Boudinot P (2007) Costimulatory receptors in jawed vertebrates: conserved CD28, odd CTLA4 and multiple BTLAs. Dev Comp Immunol 31:255–271CrossRefGoogle Scholar
  8. 8.
    Abdalla SA, Horiuchi H, Furusawa S, Matsuda H (2004) Molecular cloning and characterization of chicken tumor necrosis factor (TNF)-superfamily ligands, CD30L and TNF-related apoptosis inducing ligand (TRAIL). J Vet Med Sci 66:643–650CrossRefGoogle Scholar
  9. 9.
    Burgess SC, Young JR, Baaten BJ, Hunt L, Ross LN, Parcells MS, Kumar PM, Tregaskes CA, Lee LF, Davison TF (2004) Marek’s disease is a natural model for lymphomas overexpressing Hodgkin’s disease antigen (CD30). Proc Natl Acad Sci USA 101:13879–13884CrossRefGoogle Scholar
  10. 10.
    Sutton KM, Hu T, Wu Z, Siklodi B, Vervelde L, Kaiser P (2015) The functions of the avian receptor activator of NF-kappaB ligand (RANKL) and its receptors, RANK and osteoprotegerin, are evolutionarily conserved. Dev Comp Immunol 51:170–184CrossRefGoogle Scholar
  11. 11.
    Tregaskes CA, Glansbeek HL, Gill AC, Hunt LG, Burnside J, Young JR (2005) Conservation of biological properties of the CD40 ligand, CD154 in a non-mammalian vertebrate. Dev Comp Immunol 29:361–374CrossRefGoogle Scholar
  12. 12.
    Grant EJ, Chen L, Quinones-Parra S, Pang K, Kedzierska K, Chen W (2014) T-cell immunity to influenza A viruses. Crit Rev Immunol 34:15–39CrossRefGoogle Scholar
  13. 13.
    Kreijtz JH, Fouchier RA, Rimmelzwaan GF (2011) Immune responses to influenza virus infection. Virus Res 162:19–30CrossRefGoogle Scholar
  14. 14.
    Rauf A, Khatri M, Murgia MV, Saif YM (2012) Fas/FasL and perforin-granzyme pathways mediated T cell cytotoxic responses in infectious bursal disease virus infected chickens. Results Immunol 2:112–119CrossRefGoogle Scholar
  15. 15.
    Rauf A, Khatri M, Murgia MV, Saif YM (2011) Expression of perforin-granzyme pathway genes in the bursa of infectious bursal disease virus-infected chickens. Dev Comp Immunol 35:620–627CrossRefGoogle Scholar
  16. 16.
    Wang X, Rosa AJ, Oliverira HN, Rosa GJ, Guo X, Travnicek M, Girshick T (2006) Transcriptome of local innate and adaptive immunity during early phase of infectious bronchitis viral infection. Viral Immunol 19:768–774CrossRefGoogle Scholar
  17. 17.
    Sarson AJ, Abdul-Careem MF, Read LR, Brisbin JT, Sharif S (2008) Expression of cytotoxicity-associated genes in Marek’s disease virus-infected chickens. Viral Immunol 21:267–272CrossRefGoogle Scholar
  18. 18.
    Garcia-Camacho L, Schat KA, Brooks R Jr, Bounous DI (2003) Early cell-mediated immune responses to Marek’s disease virus in two chicken lines with defined major histocompatibility complex antigens. Vet Immunol Immunopathol 95:145–153CrossRefGoogle Scholar
  19. 19.
    Babon JA, Cruz J, Ennis FA, Yin L, Terajima M (2012) A human CD4+ T cell epitope in the influenza hemagglutinin is cross-reactive to influenza A virus subtypes and to influenza B virus. J Virol 86:9233–9243CrossRefGoogle Scholar
  20. 20.
    DiPiazza A, Richards KA, Knowlden ZA, Nayak JL, Sant AJ (2016) The role of CD4 T cell memory in generating protective immunity to novel and potentially pandemic strains of influenza. Front Immunol 7:10CrossRefGoogle Scholar
  21. 21.
    Brown DM, Lampe AT, Workman AM (2016) The differentiation and protective function of cytolytic CD4 T cells in influenza infection. Front Immunol 7:93CrossRefGoogle Scholar
  22. 22.
    Jelley-Gibbs DM, Strutt TM, McKinstry KK, Swain SL (2008) Influencing the fates of CD4 T cells on the path to memory: lessons from influenza. Immunol Cell Biol 86:343–352CrossRefGoogle Scholar
  23. 23.
    Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173CrossRefGoogle Scholar
  24. 24.
    Degen WG, Daal N, Rothwell L, Kaiser P, Schijns VE (2005) Th1/Th2 polarization by viral and helminth infection in birds. Vet Microbiol 105:163–167CrossRefGoogle Scholar
  25. 25.
    Kaiser P, Poh TY, Rothwell L, Avery S, Balu S, Pathania US, Hughes S, Goodchild M, Morrell S, Watson M, Bumstead N, Kaufman J, Young JR (2005) A genomic analysis of chicken cytokines and chemokines. J Interferon Cytokine Res 25:467–484CrossRefGoogle Scholar
  26. 26.
    Zhang L, Liu R, Song M, Hu Y, Pan B, Cai J, Wang M (2013) Eimeria tenella: interleukin 17 contributes to host immunopathology in the gut during experimental infection. Exp Parasitol 133:121–130CrossRefGoogle Scholar
  27. 27.
    Walliser I, Gobel TW (2018) Chicken IL-17A is expressed in αβ and γδ T cell subsets and binds to a receptor present on macrophages, and T cells. Dev Comp Immunol 81:44–53CrossRefGoogle Scholar
  28. 28.
    Walliser I, Gobel TW (2017) Generation of glycosylphosphatidylinositol linked chicken IL-17 to generate specific monoclonal antibodies applicable for intracellular cytokine staining. Dev Comp Immunol 73:27–35CrossRefGoogle Scholar
  29. 29.
    Shanmugasundaram R, Selvaraj RK (2011) Regulatory T cell properties of chicken CD4+ CD25+ cells. J Immunol 186:1997–2002CrossRefGoogle Scholar
  30. 30.
    Gurung A, Kamble N (2017) Association of Marek’s disease induced immunosuppression with activation of a novel regulatory T cells in chickens. PLoS Pathog 13:e1006745CrossRefGoogle Scholar
  31. 31.
    Haghighi HR, Read LR, Haeryfar SM, Behboudi S, Sharif S (2009) Identification of a dual-specific T cell epitope of the hemagglutinin antigen of an h5 avian influenza virus in chickens. PLoS One 4:e7772CrossRefGoogle Scholar
  32. 32.
    Reemers SS, van Haarlem DA, Sijts AJ, Vervelde L, Jansen CA (2012) Identification of novel avian influenza virus derived CD8+ T-cell epitopes. PLoS One 7:e31953CrossRefGoogle Scholar
  33. 33.
    Tan L, Zhang Y, Liu F, Yuan Y, Zhan Y, Sun Y, Qiu X, Meng C, Song C, Ding C (2016) Infectious bronchitis virus poly-epitope-based vaccine protects chickens from acute infection. Vaccine 34:5209–5216CrossRefGoogle Scholar
  34. 34.
    Mittendorf EA, Storrer CE, Shriver CD, Ponniah S, Peoples GE (2005) Evaluation of the CD107 cytotoxicity assay for the detection of cytolytic CD8+ cells recognizing HER2/neu vaccine peptides. Breast Cancer Res Treat 92:85–93CrossRefGoogle Scholar
  35. 35.
    Zhao M, Liu K, Luo J, Tan S, Quan C, Zhang S, Chai Y, Qi J, Li Y, Bi Y, Xiao H, Wong G, Zhou J, Jiang T, Liu W, Yu H, Yan J, Liu Y, Shu Y, Wu G, Wu A, Gao GF, Liu WJ (2018) Heterosubtypic protections against human-infecting avian influenza viruses correlate to biased cross-T-cell responses. mBio 9:e01408–e01418Google Scholar
  36. 36.
    Du CL, Xu K, Min ZH, Li DD, Yuan HL, Liu C, Chen ZH (2017) Cytokine profiles of CD4(+) T memory cells in asthma and their relationship with asthma severity. Zhonghua yi xue za zhi 97:2333–2337Google Scholar
  37. 37.
    Chen L, Anthony A, Oveissi S, Huang M, Zanker D, Xiao K, Wu C, Zou Q, Chen W (2017) Broad-Based CD4(+) T cell responses to influenza a virus in a healthy individual who lacks typical immunodominance hierarchy. Front Immunol 8:375CrossRefGoogle Scholar
  38. 38.
    Tan L, Liao Y, Fan J, Zhang Y, Mao X, Sun Y, Song C, Qiu X, Meng C, Ding C (2016) Prediction and identification of novel IBV S1 protein derived CTL epitopes in chicken. Vaccine 34:380–386CrossRefGoogle Scholar
  39. 39.
    Kaufman J, Volk H, Wallny HJ (1995) A “minimal essential Mhc” and an “unrecognized Mhc”: two extremes in selection for polymorphism. Immunol Rev 143:63–88CrossRefGoogle Scholar
  40. 40.
    Vainio O, Veromaa T, Eerola E, Toivanen P, Ratcliffe MJ (1988) Antigen-presenting cell-T cell interaction in the chicken is MHC class II antigen restricted. J Immunol 140:2864–2868Google Scholar
  41. 41.
    Guillemot F, Billault A, Pourquie O, Behar G, Chausse AM, Zoorob R, Kreibich G, Auffray C (1988) A molecular map of the chicken major histocompatibility complex: the class II beta genes are closely linked to the class I genes and the nucleolar organizer. EMBO J 7:2775–2785CrossRefGoogle Scholar
  42. 42.
    Vainio O, Koch C, Toivanen A (1984) B-L antigens (class II) of the chicken major histocompatibility complex control T-B cell interaction. Immunogenetics 19:131–140CrossRefGoogle Scholar
  43. 43.
    Briles WE, Mc GW, Irwin MR (1950) On multiple alleles effecting cellular antigens in the chicken. Genetics 35:633–652Google Scholar
  44. 44.
    Koch M, Camp S, Collen T, Avila D, Salomonsen J, Wallny HJ, van Hateren A, Hunt L, Jacob JP, Johnston F, Marston DA, Shaw I, Dunbar PR, Cerundolo V, Jones EY, Kaufman J (2007) Structures of an MHC class I molecule from B21 chickens illustrate promiscuous peptide binding. Immunity 27:885–899CrossRefGoogle Scholar
  45. 45.
    Wallny HJ, Avila D, Hunt LG, Powell TJ, Riegert P, Salomonsen J, Skjodt K, Vainio O, Vilbois F, Wiles MV, Kaufman J (2006) Peptide motifs of the single dominantly expressed class I molecule explain the striking MHC-determined response to Rous sarcoma virus in chickens. Proc Natl Acad Sci USA 103:1434–1439CrossRefGoogle Scholar
  46. 46.
    Zhou H, Lamont SJ (2003) Chicken MHC class I and II gene effects on antibody response kinetics in adult chickens. Immunogenetics 55:133–140CrossRefGoogle Scholar
  47. 47.
    Liu W, Miller MM, Lamont SJ (2002) Association of MHC class I and class II gene polymorphisms with vaccine or challenge response to Salmonella enteritidis in young chicks. Immunogenetics 54:582–590CrossRefGoogle Scholar
  48. 48.
    Juul-Madsen HR, Dalgaard TS, Rontved CM, Jensen KH, Bumstead N (2006) Immune response to a killed infectious bursal disease virus vaccine in inbred chicken lines with different major histocompatibility complex haplotypes. Poult Sci 85:986–998CrossRefGoogle Scholar
  49. 49.
    Juul-Madsen HR, Nielsen OL, Krogh-Maibom T, Rontved CM, Dalgaard TS, Bumstead N, Jorgensen PH (2002) Major histocompatibility complex-linked immune response of young chickens vaccinated with an attenuated live infectious bursal disease virus vaccine followed by an infection. Poult Sci 81:649–656CrossRefGoogle Scholar
  50. 50.
    Miller MM, Taylor RL Jr (2016) Brief review of the chicken major histocompatibility complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance. Poult Sci 95:375–392CrossRefGoogle Scholar
  51. 51.
    Banat GR, Tkalcic S, Dzielawa JA, Jackwood MW, Saggese MD, Yates L, Kopulos R, Briles WE, Collisson EW (2013) Association of the chicken MHC B haplotypes with resistance to avian coronavirus. Dev Comp Immunol 39:430–437CrossRefGoogle Scholar
  52. 52.
    Briles WE, Briles RW (1982) Identification of haplotypes of the chicken major histocompatibility complex (B). Immunogenetics 15:449–459CrossRefGoogle Scholar
  53. 53.
    Lambrecht B, Gonze M, Meulemans G, van den Berg TP (2004) Assessment of the cell-mediated immune response in chickens by detection of chicken interferon-gamma in response to mitogen and recall Newcastle disease viral antigen stimulation. Avian Pathol J WVPA 33:343–350CrossRefGoogle Scholar
  54. 54.
    Dunnington EA, Larsen CT, Gross WB, Siegel PB (1992) Antibody responses to combinations of antigens in white Leghorn chickens of different background genomes and major histocompatibility complex genotypes. Poult Sci 71:1801–1806CrossRefGoogle Scholar
  55. 55.
    Heinzelmann EW, Clark KK, Collins WM, Briles WE (1981) Host age and major histocompatibility genotype influence on Rous sarcoma regression in chickens. Poult Sci 60:2171–2175CrossRefGoogle Scholar
  56. 56.
    Joiner KS, Hoerr FJ, Ewald SJ, van Santen VL, Wright JC, van Ginkel FW, Toro H (2007) Pathogenesis of infectious bronchitis virus in vaccinated chickens of two different major histocompatibility B complex genotypes. Avian Dis 51:758–763CrossRefGoogle Scholar
  57. 57.
    Kim DK, Lillehoj HS, Hong YH, Park DW, Lamont SJ, Han JY, Lillehoj EP (2008) Immune-related gene expression in two B-complex disparate genetically inbred Fayoumi chicken lines following Eimeria maxima infection. Poult Sci 87:433–443CrossRefGoogle Scholar
  58. 58.
    Lamont SJ (1998) Impact of genetics on disease resistance. Poult Sci 77:1111–1118CrossRefGoogle Scholar
  59. 59.
    Mays JK, Bacon LD, Pandiri AR, Fadly AM (2005) Response of white leghorn chickens of various B haplotypes to infection at hatch with subgroup J avian leukosis virus. Avian Dis 49:214–219CrossRefGoogle Scholar
  60. 60.
    Yoo BH, Sheldon BL (1992) Association of the major histocompatibility complex with avian leukosis virus infection in chickens. Br Poult Sci 33:613–620CrossRefGoogle Scholar
  61. 61.
    Hofmann A, Plachy J, Hunt L, Kaufman J, Hala K (2003) v-src oncogene-specific carboxy-terminal peptide is immunoprotective against Rous sarcoma growth in chickens with MHC class I allele B-F12. Vaccine 21:4694–4699CrossRefGoogle Scholar
  62. 62.
    Kapczynski DR, Liljebjelke K, Kulkarni G, Hunt H, Jiang HJ, Petkov D (2011) Cross reactive cellular immune responses in chickens previously exposed to low pathogenic avian influenza. BMC Proc 5(Suppl 4):S13CrossRefGoogle Scholar
  63. 63.
    Seo SH, Peiris M, Webster RG (2002) Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-like H5N1 influenza virus is correlated with the proportion of pulmonary CD8(+) T cells expressing gamma interferon. J Virol 76:4886–4890CrossRefGoogle Scholar
  64. 64.
    Seo SH, Webster RG (2001) Cross-reactive, cell-mediated immunity and protection of chickens from lethal H5N1 influenza virus infection in Hong Kong poultry markets. J Virol 75:2516–2525CrossRefGoogle Scholar
  65. 65.
    Wang F, Wang X, Chen H, Liu J, Cheng Z (2011) The critical time of avian leukosis virus subgroup J-mediated immunosuppression during early stage infection in specific pathogen-free chickens. J Vet Sci 12:235–241CrossRefGoogle Scholar
  66. 66.
    Xu Q, Cui N, Ma X, Wang F, Li H, Shen Z, Zhao X (2016) Evaluation of a chimeric multi-epitope-based DNA vaccine against subgroup J avian leukosis virus in chickens. Vaccine 34:3751–3756CrossRefGoogle Scholar
  67. 67.
    Wang Y, Wang G, Wang Z, Zhang H, Zhang L, Cheng Z (2014) Chicken biliary exosomes enhance CD4(+)T proliferation and inhibit ALV-J replication in liver. Biochem Cell Biol 92:145–151CrossRefGoogle Scholar
  68. 68.
    Butter C, Staines K, van Hateren A, Davison TF, Kaufman J (2013) The peptide motif of the single dominantly expressed class I molecule of the chicken MHC can explain the response to a molecular defined vaccine of infectious bursal disease virus (IBDV). Immunogenetics 65:609–618CrossRefGoogle Scholar
  69. 69.
    Hou Y, Guo Y, Wu C, Shen N, Jiang Y, Wang J (2012) Prediction and identification of T cell epitopes in the H5N1 influenza virus nucleoprotein in chicken. PLoS One 7:e39344CrossRefGoogle Scholar
  70. 70.
    Zhang W, Huang Q, Lu M, Zhu F, Huang YY, Yang SH, Kong Z, Zhang XM, Xu CT (2016) Exploration of the BF2*15 major histocompatibility complex class I binding motif and identification of cytotoxic T lymphocyte epitopes from the H5N1 influenza virus nucleoprotein in chickens. Adv Virol 161:3081–3093Google Scholar
  71. 71.
    Zhu FZ, Lu M, Huang QH, Huang YY, Yang SH, Cui YS, Liu C, Tan L, Kong Z, Xu CT (2016) Interactive mechanism between avian infectious bronchitis S1 protein T cell peptide and avian MHC I molecule. Virus Res 215:76–83CrossRefGoogle Scholar
  72. 72.
    Chen L, Zanker D, Xiao K, Wu C, Zou Q, Chen W (2014) Immunodominant CD4+ T-cell responses to influenza A virus in healthy individuals focus on matrix 1 and nucleoprotein. J Virol 88:11760–11773CrossRefGoogle Scholar
  73. 73.
    Grant E, Wu C, Chan KF, Eckle S, Bharadwaj M, Zou QM, Kedzierska K, Chen W (2013) Nucleoprotein of influenza A virus is a major target of immunodominant CD8+ T-cell responses. Immunol Cell Biol 91:184–194CrossRefGoogle Scholar
  74. 74.
    Wu C, Zanker D, Valkenburg S, Tan B, Kedzierska K, Zou QM, Doherty PC, Chen W (2011) Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals. Proc Natl Acad Sci USA 108:9178–9183CrossRefGoogle Scholar
  75. 75.
    Yan RQ, Wu ZM, Fang QM, Zhang ZL, Zhang J, Li XS, Hao HF, Xia C (2008) Reconstruction of a chicken BF2 protein complex and identification of binding nonamer peptides derived from avian influenza virus hemagglutinin. Vet Immunol Immunopathol 126:91–101CrossRefGoogle Scholar
  76. 76.
    Ignjatovic J, Sapats S (2005) Identification of previously unknown antigenic epitopes on the S and N proteins of avian infectious bronchitis virus. Adv Virol 150:1813–1831Google Scholar
  77. 77.
    Boots AM, Kusters JG, van Noort JM, Zwaagstra KA, Rijke E, van der Zeijst BA, Hensen EJ (1991) Localization of a T-cell epitope within the nucleocapsid protein of avian coronavirus. Immunology 74:8–13Google Scholar
  78. 78.
    Wei Y, Qi L, Gao H, Sun H, Pu J, Sun Y, Liu J (2016) Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine. Sci Rep 6:30382CrossRefGoogle Scholar
  79. 79.
    Spackman E, Pantin-Jackwood MJ (2014) Practical aspects of vaccination of poultry against avian influenza virus. Vet J (Lond, Engl: 1997) 202:408–415CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouPeople’s Republic of China
  2. 2.T Cell Lab, Department of Biochemistry and Genetics, La Trobe Institute of Molecular ScienceLa Trobe UniversityBundooraAustralia
  3. 3.National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and ControlGuangzhouPeople’s Republic of China
  4. 4.Key Laboratory of Veterinary Vaccine Innovation of the Ministry of AgricultureGuangzhouPeople’s Republic of China
  5. 5.Key Laboratory of Zoonosis Prevention and Control of Guangdong ProvinceGuangzhouPeople’s Republic of China

Personalised recommendations