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Home / Equine Research Bank / J Virol / Major histocompatibility complex class I-restricted cytotoxi...
Journal of virology1995; 69(1); 606-612; doi: 10.1128/JVI.69.1.606-612.1995

Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte responses in horses infected with equine herpesvirus 1.

Abstract: An experimental system that permits sensitive and reproducible detection of equine herpesvirus 1 (EHV-1)-specific cytotoxic T-lymphocyte (CTL) activity in the horse was developed. Peripheral blood mononuclear cells (PBMC) collected from immune horses were restimulated in vitro by culture with live EHV-1. Cytotoxic activity against virus-infected, pokeweed mitogen-stimulated lymphoblast targets was assessed in a 4-h 51Cr release assay. The optimal conditions for in vitro stimulation of equine memory CTLs and for preparation of EHV-1-infected target cells expressing viral antigens were systematically identified by individually testing the effects of variations in responder cell concentration, culture medium composition, serum type, incubation time, antigen form, and exogenous mediator content. By using this optimized system for generation and assay of equine CTLs, the development of EHV-1-specific cytotoxic responses in 12 horses was evaluated after experimental viral infection. CTLs with the capacity for killing EHV-1-infected target cells were detected in equine PBMC as early as 1 week postinfection, reached maximal levels by 2 to 3 weeks, and remained detectable for a year after infection. Equine effector cells mediating lysis of EHV-1-infected targets were predominantly CD8+ T lymphocytes, and the cytotoxicity was specific for virus and restricted by major histocompatibility complex class I molecules. The results define a reliable and convenient experimental system for generation and assay of EHV-1 CTLs which can now be used for more-detailed characterization of the equine CTL response to infection by this herpesvirus pathogen.
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Publication Date: 1995-01-01 PubMed ID: 7983765PubMed Central: PMC188619DOI: 10.1128/JVI.69.1.606-612.1995Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study discusses the creation of an experimental system for the sensitive and accurate detection of equine herpesvirus 1 (EHV-1)-specific cytotoxic T-lymphocyte (CTL) activity in horses. The article also explores how CTLs, which are crucial for killing infected cells, can develop and respond to EHV-1 infection.

Design of Experiment

  • The researchers developed a system to detect and measure Equine herpesvirus 1 (EHV-1) specific cytotoxic T lymphocytes (CTLs) in horses. This involved the collection of Peripheral blood mononuclear cells (PBMC) from veteran horses, which were later cultured with live EHV-1.
  • The cytotoxic activity against EHV-1-infected cells was assessed using a 51Cr release assay over a 4-hour period. This allowed the team to determine how well the CTLs were able to destroy infected cells.

Optimization of Experimental Conditions

  • The team systematically identified the optimal conditions for memory CTL stimulation and the preparation of EHV-1-infected cells.
  • This involved testing various aspects such as the concentration of responder cells, the composition of the culture medium, the type of serum used, incubation time, antigen form, and the content of exogenous mediators.

Development and Evaluation of CTL Responses

  • Using this optimized system, the team assessed the development of EHV-1-specific CTL responses in 12 horses following experimental viral infection.
  • They discovered that CTLs capable of destroying EHV-1-infected cells were detectable in horse PBMC as early as 1 week post-infection. Their levels peaked by the 2nd or 3rd week and remained detectable for a year following the infection.

Characteristics of CTLs

  • Upon further examination, the researchers found that the effector cells mediating the lysis of EHV-1 infected cells were predominantly CD8+ T lymphocytes.
  • Furthermore, they discovered that the cytotoxicity was limited to the virus and was restricted by the so-called major histocompatibility complex class I molecules. This demonstrates the specificity and selectivity of the immune response triggered by EHV-1 infection.

Conclusion & Implications

  • The findings from this study have established a reliable system for generating and assaying EHV-1 specific CTLs. This can now be used to further study and understand the equine CTL response to this particular pathogen.
  • Given that EHV-1 is a common virus affecting horses, this research has valuable implications for improving our understanding of equine immune responses and potentially informing future treatment strategies.

Cite This Article

APA
Allen G, Yeargan M, Costa LR, Cross R. (1995). Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte responses in horses infected with equine herpesvirus 1. J Virol, 69(1), 606-612. https://doi.org/10.1128/JVI.69.1.606-612.1995

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 69
Issue: 1
Pages: 606-612

Researcher Affiliations

Allen, G
  • Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546.
Yeargan, M
    Costa, L R
      Cross, R

        MeSH Terms

        • Animals
        • Cytotoxicity, Immunologic
        • Female
        • Herpesviridae Infections / blood
        • Herpesviridae Infections / immunology
        • Herpesviridae Infections / veterinary
        • Herpesvirus 1, Equid / immunology
        • Histocompatibility Antigens Class I / immunology
        • Horses
        • Lymphocyte Activation
        • T-Lymphocytes, Cytotoxic / immunology

        References

        This article includes 28 references
        1. Chowdhury SI, Kubin G, Ludwig H. Equine herpesvirus type 1 (EHV-1) induced abortions and paralysis in a Lipizzaner stud: a contribution to the classification of equine herpesviruses.. Arch Virol 1986;90(3-4):273-88.
          pubmed: 3015084doi: 10.1007/BF01317376google scholar: lookup
        2. Allen GP. The Equine Virology Research Foundation--a view from abroad.. Equine Vet J 1994 Jul;26(4):259-62.
          pubmed: 8575392doi: 10.1111/j.2042-3306.1994.tb04385.xgoogle scholar: lookup
        3. Dutta SK, Campbell DL. Cell mediated immunity in equine herpesvirus type 1 infection I. In vitro lymphocyte blastogenesis and serum neutralization antibody in normal parturient and aborting mares.. Can J Comp Med 1977 Oct;41(4):404-8.
          pubmed: 200317
        4. Jackson T, Kendrick JW. Paralysis of horses associated with equine herpesvirus 1 infection.. J Am Vet Med Assoc 1971 Apr 15;158(8):1351-7.
          pubmed: 4328999
        5. Bailey E. Identification and genetics of horse lymphocyte alloantigens.. Immunogenetics 1980;11(5):499-506.
          pubmed: 6242885doi: 10.1007/BF01567818google scholar: lookup
        6. Greenwood RE, Simson AR. Clinical report of a paralytic syndrome affecting stallions, mares and foals on a thoroughbred studfarm.. Equine Vet J 1980 Jul;12(3):113-7.
          pubmed: 6250820doi: 10.1111/j.2042-3306.1980.tb03397.xgoogle scholar: lookup
        7. Whitwell KE, Blunden AS. Pathological findings in horses dying during an outbreak of the paralytic form of Equid herpesvirus type 1 (EHV-1) infection.. Equine Vet J 1992 Jan;24(1):13-9.
          pubmed: 1313358doi: 10.1111/j.2042-3306.1992.tb02771.xgoogle scholar: lookup
        8. Mumford JA, Bates J. Trials of an inactivated equid herpesvirus 1 vaccine: challenge with a subtype 2 virus.. Vet Rec 1984 Apr 14;114(15):375-81.
          pubmed: 6328729doi: 10.1136/vr.114.15.375google scholar: lookup
        9. Allen GP, Bryans JT. Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections.. Prog Vet Microbiol Immunol 1986;2:78-144.
          pubmed: 2856183
        10. Bürki F, Rossmanith W, Nowotny N, Pallan C, Möstl K, Lussy H. Viraemia and abortions are not prevented by two commercial equine herpesvirus-1 vaccines after experimental challenge of horses.. Vet Q 1990 Apr;12(2):80-6.
          pubmed: 2163560doi: 10.1080/01652176.1990.9694249google scholar: lookup
        11. Bailey E. Population studies on the ELA system in American standardbred and thoroughbred mares.. Anim Blood Groups Biochem Genet 1983;14(3):201-11.
          pubmed: 6660596doi: 10.1111/j.1365-2052.1983.tb01073.xgoogle scholar: lookup
        12. Ostlund EN. The equine herpesviruses.. Vet Clin North Am Equine Pract 1993 Aug;9(2):283-94.
          pubmed: 8395324doi: 10.1016/s0749-0739(17)30396-6google scholar: lookup
        13. Scott JC, Dutta SK, Myrup AC. In vivo harboring of equine herpesvirus-1 in leukocyte populations and subpopulations and their quantitation from experimentally infected ponies.. Am J Vet Res 1983 Jul;44(7):1344-8.
          pubmed: 6309042
        14. Burrows R, Goodridge D, Denyer MS. Trials of an inactivated equid herpesvirus 1 vaccine: challenge with a subtype 1 virus.. Vet Rec 1984 Apr 14;114(15):369-74.
          pubmed: 6328728doi: 10.1136/vr.114.15.369google scholar: lookup
        15. Gibson JS, O'Neill T, Thackray A, Hannant D, Field HJ. Serological responses of specific pathogen-free foals to equine herpesvirus-1: primary and secondary infection, and reactivation.. Vet Microbiol 1992 Oct;32(3-4):199-214.
          pubmed: 1333670doi: 10.1016/0378-1135(92)90145-jgoogle scholar: lookup
        16. Campos M, Rossi CR. In vitro induction of cytotoxic lymphocytes from infectious bovine rhinotracheitis virus hyperimmune cattle.. Am J Vet Res 1986 Nov;47(11):2411-4.
          pubmed: 3024535
        17. Edington N, Smyth B, Griffiths L. The role of endothelial cell infection in the endometrium, placenta and foetus of equid herpesvirus 1 (EHV-1) abortions.. J Comp Pathol 1991 May;104(4):379-87.
          pubmed: 1651960doi: 10.1016/s0021-9975(08)80148-xgoogle scholar: lookup
        18. Bürki F, Nowotny N, Oulehla J, Schmehlik O, Möstl K, Pallan C, Rossmanith E. Attempts to immunoprotect adult horses, specifically pregnant mares, with commercial vaccines against clinical disease induced by equine herpesvirus-1.. Zentralbl Veterinarmed B 1991 Aug;38(6):432-40.
          pubmed: 1659067doi: 10.1111/j.1439-0450.1991.tb00892.xgoogle scholar: lookup
        19. Gibson JS, Slater JD, Awan AR, Field HJ. Pathogenesis of equine herpesvirus-1 in specific pathogen-free foals: primary and secondary infections and reactivation.. Arch Virol 1992;123(3-4):351-66.
          pubmed: 1314051doi: 10.1007/BF01317269google scholar: lookup
        20. Antczak DF, Bailey E, Barger B, Guerin G, Lazary S, McClure J, Mottironi VD, Symons R, Templeton J, Varewyck H. Joint report of the Third International Workshop on Lymphocyte Alloantigens of the Horse, Kennett Square, Pennsylvania, 25-27 April 1984.. Anim Genet 1986;17(4):363-73.
          pubmed: 3826760doi: 10.1111/j.1365-2052.1986.tb00730.xgoogle scholar: lookup
        21. Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.. Arch Virol 1986;90(1-2):111-24.
          pubmed: 3015074doi: 10.1007/BF01314149google scholar: lookup
        22. Song W, Collisson EW, Billingsley PM, Brown WC. Induction of feline immunodeficiency virus-specific cytolytic T-cell responses from experimentally infected cats.. J Virol 1992 Sep;66(9):5409-17.
          pubmed: 1323704doi: 10.1128/JVI.66.9.5409-5417.1992google scholar: lookup
        23. Bryans JT. On immunity to disease caused by equine herpesvirus 1.. J Am Vet Med Assoc 1969 Jul 15;155(2):294-300.
          pubmed: 4307796
        24. Crowhurst FA, Dickinson G, Burrows R. An outbreak of paresis in mares and geldings associated with equid herpesvirus 1.. Vet Rec 1981 Dec 12;109(24):527-8.
          pubmed: 6280366
        25. Crabb BS, Allen GP, Studdert MJ. Characterization of the major glycoproteins of equine herpesviruses 4 and 1 and asinine herpesvirus 3 using monoclonal antibodies.. J Gen Virol 1991 Sep;72 ( Pt 9):2075-82.
          pubmed: 1716650doi: 10.1099/0022-1317-72-9-2075google scholar: lookup
        26. Splitter GA, Eskra L, Abruzzini AF. Cloned bovine cytolytic T cells recognize bovine herpes virus-1 in a genetically restricted, antigen-specific manner.. Immunology 1988 Jan;63(1):145-50.
          pubmed: 2448231
        27. DOLL ER, CROWE ME, BRYANS JT, McCOLLUM WH. Infection immunity in equine virus abortion.. Cornell Vet 1955 Jul;45(3):387-410.
          pubmed: 14390961
        28. Smith KC, Whitwell KE, Mumford JA, Gower SM, Hannant D, Tearle JP. An immunohistological study of the uterus of mares following experimental infection by equid herpesvirus 1.. Equine Vet J 1993 Jan;25(1):36-40.
          pubmed: 8380768doi: 10.1111/j.2042-3306.1993.tb02898.xgoogle scholar: lookup

        Citations

        This article has been cited 22 times.
        1. Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B. An Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame 2 Deletion Mutant Provides Immunity and Protection from EHV-1 Infection and Disease.. J Virol 2019 Nov 15;93(22).
          doi: 10.1128/JVI.01011-19pubmed: 31462575google scholar: lookup
        2. Kim SK, Shakya AK, O'Callaghan DJ. Intranasal treatment with CpG-B oligodeoxynucleotides protects CBA mice from lethal equine herpesvirus 1 challenge by an innate immune response.. Antiviral Res 2019 Sep;169:104546.
          doi: 10.1016/j.antiviral.2019.104546pubmed: 31247247google scholar: lookup
        3. Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L, Van den Broeck W, Azab W, Nauwynck HJ. Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs.. J Virol 2019 Apr 1;93(7).
          doi: 10.1128/JVI.02098-18pubmed: 30651370google scholar: lookup
        4. Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H, Watts C, Rollins A, Osterrieder N, Wagner B. Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity.. BMC Vet Res 2018 Aug 22;14(1):245.
          doi: 10.1186/s12917-018-1563-4pubmed: 30134896google scholar: lookup
        5. Liu SA, Stanfield BA, Chouljenko VN, Naidu S, Langohr I, Del Piero F, Ferracone J, Roy AA, Kousoulas KG. Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice.. J Virol 2017 Jun 15;91(12).
          doi: 10.1128/JVI.02445-16pubmed: 28404844google scholar: lookup
        6. Kim SK, Shakya AK, O'Callaghan DJ. Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge.. J Virol 2016 Sep 15;90(18):8090-104.
          doi: 10.1128/JVI.00986-16pubmed: 27356904google scholar: lookup
        7. Bergmann T, Moore C, Sidney J, Miller D, Tallmadge R, Harman RM, Oseroff C, Wriston A, Shabanowitz J, Hunt DF, Osterrieder N, Peters B, Antczak DF, Sette A. The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires.. Immunogenetics 2015 Nov;67(11-12):675-89.
          doi: 10.1007/s00251-015-0872-zpubmed: 26399241google scholar: lookup
        8. Goodman LB, Wimer C, Dubovi EJ, Gold C, Wagner B. Immunological correlates of vaccination and infection for equine herpesvirus 1.. Clin Vaccine Immunol 2012 Feb;19(2):235-41.
          doi: 10.1128/CVI.05522-11pubmed: 22205656google scholar: lookup
        9. Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011 Feb 7;42(1):23.
          doi: 10.1186/1297-9716-42-23pubmed: 21314906google scholar: lookup
        10. Wagner B, Burton A, Ainsworth D. Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals.. Vet Res 2010 Jul-Aug;41(4):47.
          doi: 10.1051/vetres/2010019pubmed: 20374696google scholar: lookup
        11. Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA. Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route.. Vaccine 2007 Oct 23;25(43):7582-97.
          doi: 10.1016/j.vaccine.2007.07.055pubmed: 17889970google scholar: lookup
        12. Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Cloning and large-scale expansion of epitope-specific equine cytotoxic T lymphocytes using an anti-equine CD3 monoclonal antibody and human recombinant IL-2.. Vet Immunol Immunopathol 2007 Jul 15;118(1-2):121-8.
          doi: 10.1016/j.vetimm.2007.04.001pubmed: 17498813google scholar: lookup
        13. Molinková D, Celer V. Recombinant single chain Fv antibodies specific for glycoprotein D of equid herpesvirus 1.. Folia Microbiol (Praha) 2006;51(5):492-6.
          doi: 10.1007/BF02931597pubmed: 17176773google scholar: lookup
        14. Fraser DG, Leib SR, Zhang BS, Mealey RH, Brown WC, McGuire TC. Lymphocyte proliferation responses induced to broadly reactive Th peptides did not protect against equine infectious anemia virus challenge.. Clin Diagn Lab Immunol 2005 Aug;12(8):983-93.
          doi: 10.1128/CDLI.12.8.983-993.2005pubmed: 16085917google scholar: lookup
        15. Kohler AK, Stone DM, Hines MT, Byrne BA, Alperin DC, Norton LK, Hines SA. Rhodococcus equi secreted antigens are immunogenic and stimulate a type 1 recall response in the lungs of horses immune to R. equi infection.. Infect Immun 2003 Nov;71(11):6329-37.
          doi: 10.1128/IAI.71.11.6329-6337.2003pubmed: 14573652google scholar: lookup
        16. Fraser DG, Mealey RH, McGuire TC. Selecting peptides to optimize Th1 responses to an equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides.. Immunogenetics 2003 Oct;55(7):508-14.
          doi: 10.1007/s00251-003-0600-ypubmed: 12942208google scholar: lookup
        17. Castillo-Olivares J, Wieringa R, Bakonyi T, de Vries AA, Davis-Poynter NJ, Rottier PJ. Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain.. J Virol 2003 Aug;77(15):8470-80.
          doi: 10.1128/jvi.77.15.8470-8480.2003pubmed: 12857916google scholar: lookup
        18. Fraser DG, Oaks JL, Brown WC, McGuire TC. Identification of broadly recognized, T helper 1 lymphocyte epitopes in an equine lentivirus.. Immunology 2002 Mar;105(3):295-305.
          doi: 10.1046/j.0019-2805.2001.01370.xpubmed: 11918691google scholar: lookup
        19. Zhang W, Lonning SM, McGuire TC. Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection.. J Virol 1998 Dec;72(12):9612-20.
          doi: 10.1128/JVI.72.12.9612-9620.1998pubmed: 9811694google scholar: lookup
        20. Smith PM, Zhang Y, Jennings SR, O'Callaghan DJ. Characterization of the cytolytic T-lymphocyte response to a candidate vaccine strain of equine herpesvirus 1 in CBA mice.. J Virol 1998 Jul;72(7):5366-72.
          doi: 10.1128/JVI.72.7.5366-5372.1998pubmed: 9620990google scholar: lookup
        21. Seo SH, Collisson EW. Specific cytotoxic T lymphocytes are involved in in vivo clearance of infectious bronchitis virus.. J Virol 1997 Jul;71(7):5173-7.
          doi: 10.1128/JVI.71.7.5173-5177.1997pubmed: 9188584google scholar: lookup
        22. Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC. Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.. J Virol 1997 May;71(5):3840-52.
          doi: 10.1128/JVI.71.5.3840-3852.1997pubmed: 9094660google scholar: lookup
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