Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-14T06:23:12.389Z Has data issue: false hasContentIssue false
  • English
  • Français

Cytotoxic T lymphocytes in protection against equine infectious anemia virus

Published online by Cambridge University Press:  28 February 2007

Travis C. McGuire ,
Darrilyn G. Fraser  and
Robert H. Mealey
Travis C. McGuire*
Affiliation:
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164–7040, USA
Darrilyn G. Fraser
Affiliation:
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164–7040, USA
Robert H. Mealey
Affiliation:
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164–7040, USA
*
E-mail: mcguiret@vetmed.wsu.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Cytotoxic T lymphocytes (CTL) are associated with virus control in horses infected with equine infectious anemia virus (EIAV). Early in infection, control of the initial viremia coincides with the appearance of CTL and occurs before the appearance of neutralizing antibody. In carrier horses, treatment with immunosuppressive drugs results in viremia before a change in serum neutralizing antibody occurs. Clearance of initial viremia caused by other lentiviruses, including human immunodeficiency virus-1 and simian immunodeficiency virus, is also associated with CTL and not neutralizing antibody. In addition, depletion of CD8+ cells prior to infection of rhesus monkeys with simian immunodeficiency prevents clearance of virus and the same treatment of persistently infected monkeys results in viremia. Cats given adoptive transfers of lymphocytes from vaccinated cats were protected and the protection was MHC-restricted, occurred in the absence of antiviral humoral immunity, and correlated with the transfer of cells with feline immunodeficiency virus-specific CTL and T-helper lymphocyte activities. Therefore, a lentiviral vaccine, including one for EIAV, needs to induce CTL. Based on initial failures to induce CTL to EIAV proteins by any means other than infection, we attempted to define an experimental system for the evaluation of methods for CTL induction. CTL epitopes restricted by the ELA-A1 haplotype were identified and the MHC class I molecule presenting these peptides was identified. This was done by expressing individual MHC class I molecules from cDNA clones in target cells. The target cells were then pulsed with peptides and used with effector CTL stimulated with the same peptides. In a preliminary experiment, immunization of three ELA-A1 haplotype horses with an Env peptide restricted by this haplotype resulted in CTL in peripheral blood mononuclear cells (PBMC) which recognized the Env peptide and virus-infected cells, but the CTL response was transient. Nevertheless there was significant protection against clinical disease following EIAV challenge of these immunized horses when compared with three control horses given the same virus challenge. These data indicated that responses to peptides in immunized horses needed to be enhanced. Optimal CTL responses require help from CD4+ T lymphocytes, and experiments were done to identify EIAV peptides which stimulated CD4+ T lymphocytes in PBMC from infected horses with different MHC class II types. Two broadly cross-reactive Gag peptides were identified which stimulated only an interferon γ response by CD4+ T lymphocytes, which indicated a T helper 1 response is needed for CTL stimulation. Such peptides should facilitate CTL responses; however, other problems in inducing protection against lentiviruses remain, the most significant of them being EIAV variants that can escape both CTL and neutralizing antibody. A possible solution to CTL escape variants is the induction of high-avidity CTL to multiple EIAV epitopes.

Keywords

cytotoxic T cellsequine infectious anemia virusvaccinesT-helper 1
Type
Research Article
Information
Animal Health Research Reviews , Volume 5 , Issue 2 , December 2004 , pp. 271 - 276
Copyright
Copyright © CAB International 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Amara, RR, Villinger, F, Altman, JD, Lydy, SL, O'Neil, SP, Staprans, SI, Montefiori, DC, Xu, Y, Herndon, JG, Wyatt, LS, Candido, MA, Kozyr, NL, Earl, PL, Smith, JM, Ma, HL, Grimm, BD, Hulsey, ML, McClure, HM, McNicholl, JM, Moss, B and Robinson, HL (2002). Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Vaccine 20: 1949–1955.CrossRefGoogle ScholarPubMed
Baba, TW, Jeong, YS, Pennick, D, Bronson, R, Greene, MF and Ruprecht, RM (1995). Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. Science 267: 1820–1825.CrossRefGoogle ScholarPubMed
Bailey, E (1983). Population studies on the ELA system in American Standardbred and Thoroughbred mares. Animal Blood Groups and Biochemical Genetics 14: 201–211.CrossRefGoogle ScholarPubMed
Bailey, E, Marti, E, Fraser, DG, Antczak, DF and Lazary, S (2000). Immunogenetics of the horse. In: Bowling, AT and Ruvinsky, A, editors. The Genetics of the Horse New York: CABI Publishing pp. 123–147CrossRefGoogle Scholar
Barbis, DP, Maher, JK, Stanek, J, Klaunberg, BA and Antczak, DF (1994). Horse cDNA clones encoding two MHC class I genes. Immunogenetics 40: 163.CrossRefGoogle ScholarPubMed
Barouch, DH and Letvin, NL (2002). Viral evolution and challenges in the development of HIV vaccines. Vaccine 20: A66–A68.CrossRefGoogle ScholarPubMed
Barouch, DH, Santra, S, Schmitz, JE, Kuroda, MJ, Fu, TM, Wagner, W, Bilska, M, Craiu, A, Zheng, XX, Krivulka, GR, Beaudry, K, Lifton, MA, Nickerson, CE, Trigona, WL, Punt, K, Freed, DC, Guan, L, Dubey, S, Casimiro, D, Simon, A, Davies, ME, Chastain, M, Strom, TB, Gelman, RS, Montefiori, DC, Lewis, MG, Emini, EA, Shiver, JW and Letvin, NL (2000). Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290: 486–492.CrossRefGoogle ScholarPubMed
Bernoco, D, Antczak, DF, Bailey, E, Bell, K, Bull, R, Byrns, G, Guerin, G, Lazary, S, McClure, J, Templeton, J and Varewyck, H (1987). Joint report of the Fourth International Workshop on Lymphocyte Alloantigens of the Horse. Lexington, Kentucky, 12–22 October, 1985. Animal Genetics 18: 81–94.CrossRefGoogle Scholar
Borrow, P, Lewicki, H, Hahn, BH, Shaw, GM and Oldstone, MB (1994). Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. Journal of Virology 68: 6103–6110.CrossRefGoogle ScholarPubMed
Brodie, SJ, Lewinsohn, DA, Patterson, BK, Jiyamapa, D, Krieger, J, Corey, L, Greenberg, PD and Riddell, SR (1999). In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nature Medicine 5: 34–41.CrossRefGoogle ScholarPubMed
Carpenter, S, Evans, LH, Sevoian, M and Chesebro, B (1987). Role of the host immune response in selection of equine infectious anemia variants. Journal of Virology 61: 3783–3789.CrossRefGoogle ScholarPubMed
Carpenter, S, Baker, JM, Bacon, SJ, Hopman, T, Maher, J, Ellis, SA and Antczak, DF (2001). Molecular and functional characterization of genes encoding horse MHC class I antigens. Immunogenetics 53: 802–809.CrossRefGoogle ScholarPubMed
Castelli, JC, Deeks, SG, Shiboski, S and Levy, JA (2002). Relationship of CD8(+) T cell noncytotoxic anti-HIV response to CD4(+) T cell number in untreated asymptomatic HIV-infected individuals. Blood 99: 4225–4227.CrossRefGoogle ScholarPubMed
Chung, C, Mealey, RH and McGuire, TC (2004). CTL from EIAV carrier horses with diverse MHC class alleles recognize epitope clusters in Gag matrix proteins. Virology 327: 144–154.CrossRefGoogle Scholar
Daniel, MD, Kirchhoff, F, Czajak, SC, Sehgal, PK and Desrosiers, RC (1992). Protective effects of a live attenuated SIV vaccine with a deleted nef gene. Science 258: 1938–1941.CrossRefGoogle ScholarPubMed
Egan, MA, Charini, WA, Kuroda, MJ, Schmitz, JE, Racz, P, Tenner-Racz, K, Manson, K, Wyand, M, Lifton, MA, Nickerson, CE, Fu, T, Shiver, JW and Letvin, NL (2000). Simian immunodeficiency virus (SIV) gag DNA-vaccinated rhesus monkeys develop secondary cytotoxic T-lymphocyte responses and control viral replication after pathogenic SIV infection. Journal of Virology 74: 7485–7495.CrossRefGoogle ScholarPubMed
Ellis, SA, Martin, AJ, Holmes, EC and Morrison, WI (1995). At least four MHC class I genes are transcribed in the horse: phylogenetic analysis suggests an unusual evolutionary history for the MHC in this species. European Journal of Immunogenetics 22: 249–260.CrossRefGoogle ScholarPubMed
Fraser, DG, Oaks, JL, Brown, WC and McGuire, TC (2002). Identification of broadly-recognized, Th1 lymphocyte epitopes in an equine lentivirus. Immunology 105: 295–305.CrossRefGoogle Scholar
Fraser, DG, Mealey, RH and McGuire, C (2003). Selective peptides to optimise Th1 responses to equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides. Immunogenetics 55: 503–514.CrossRefGoogle Scholar
Haase, AT, Henry, K, Zupancic, M, Sedgewick, G, Faust, RA, Melroe, H, Cavert, W, Gebhard, K, Staskus, K, Zhang, ZQ, Dailey, PJ, Balfour, HH, Erice, A and Perelson, AS (1996). Quantitative image analysis of HIV-1 infection in lymphoid tissue. Science 274: 985–989.CrossRefGoogle ScholarPubMed
Hammond, SA, Cook, SJ, Lichtenstein, DL, Issel, CJ and Montelaro, RC (1997). Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process. Journal of Virology 71: 3840–3852.CrossRefGoogle ScholarPubMed
Hammond, SA, Li, F, McKeon, BM, Cook, SJ, Issel, CJ and Montelaro, RC (2000). Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus. Journal of Virology 74: 5968–5981.CrossRefGoogle ScholarPubMed
Holmes, EC and Ellis, SA (1999). Evolutionary history of MHC class I genes in the mammalian order Perissodactyla. Journal of Molecular Evolution 49: 316–324.CrossRefGoogle ScholarPubMed
Issel, CJ, Horohov, DW, Lea, DF, Adams, WV, Hagius, SD, McManus, JM, Allison, AC and Montelaro, RC (1992). Efficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus. Journal of Virology 66: 3398–3408.CrossRefGoogle ScholarPubMed
Kaech, SM and Ahmed, R (2001). Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nature Immunology 2: 415–422.CrossRefGoogle ScholarPubMed
Koenig, S, Conley, AJ, Brewah, YA, Jones, GM, Leath, S, Boots, LJ, Davey, V, Pantaleo, G, Demarest, JF, Carter, C, Wannebo, C, Yannelli, JR, Rosenberg, SA and Lane, HC (1995). Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nature Medicine 1: 330–336.CrossRefGoogle Scholar
Kono, Y (1969). Viremia and immunological responses in horses infected with equine infectious anemia virus. National Institute of Animal Health Quarterly 9: 1–9.Google ScholarPubMed
Kono, Y, Kobayashi, K and Fukunaga, Y (1973). Antigenic drift of equine infectious anemia virus in chronically infected horses. Archiv für die Gesamte Virusforschung 41: 1–40.CrossRefGoogle ScholarPubMed
Kono, Y, Hirasawa, K, Fukunaga, Y and Taniguchi, T (1976). Recrudescence of equine infectious anemia by treatment with immunosuppressive drugs. National Institute of Animal Health Quarterly 16: 8–15.Google ScholarPubMed
Koup, RA, Safrit, JT, Cao, Y, Andrews, CA, McLeod, G, Borkowsky, W, Farthing, C and Ho, DD (1994). Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. Journal of Virology 68: 4650–4655.CrossRefGoogle ScholarPubMed
Kuroda, MJ, Schmitz, JE, Charini, WA, Nickerson, CE, Lifton, MA, Lord, CI, Forman, MA and Letvin, NL (1999). Emergence of CTL coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys. Journal of Immunology 162: 5127–5133.CrossRefGoogle ScholarPubMed
Matano, T, Shibata, R, Siemon, C, Connors, M, Lane, HC and Martin, MA (1998). Administration of an anti-CD8 monoclonal antibody interferes with the clearance of chimeric simian/human immunodeficiency virus during primary infections of rhesus macaques. Journal of Virology 72: 164–169.CrossRefGoogle ScholarPubMed
McGuire, TC, Tumas, DB, Byrne, KM, Hines, MT, Leib, SR, Brassfield, AL, O'Rourke, KI and Perryman, LE (1994). Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize env and gag/PR proteins. Journal of Virology 68: 1459–1467.CrossRefGoogle ScholarPubMed
McGuire, TC, Zhang, W, Hines, MT, Henny, PJ and Byrne, KM (1997). Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses. Virology 238: 85–93.CrossRefGoogle ScholarPubMed
McGuire, TC, Leib, SR, Lonning, SM, Zhang, W, Byrne, KM and Mealey, RM (2000). Equine infectious anaemia virus proteins with epitopes most frequently recognized by cytotoxic T lymphocytes from infected horses. Journal of General Virology 81: 2735–2739.CrossRefGoogle ScholarPubMed
McGuire, TC, Leib, SR, Mealey, RH, Fraser, DG and Prieur, DJ (2003). Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule. Journal of Immunology 171: 1984–1993.CrossRefGoogle ScholarPubMed
McKinney, DM, Lewinsohn, DA, Riddell, SR, Greenberg, PD and Mosier, DE (1999). The antiviral activity of HIV-specific CD8+ CTL clones is limited by elimination due to encounter with HIV-infected targets. Journal of Immunology. 163: 861–867.CrossRefGoogle ScholarPubMed
Mealey, RH, Fraser, DG, Oaks, JL, Cantor, GH and McGuire, TC (2001). Immune reconstitution prevents continuous equine infectious anemia virus replication in an Arabian foal with severe combined immunodeficiency: lessons for control of lentiviruses. Clinical Immunology 101: 237–247.CrossRefGoogle Scholar
Mealey, RH, Zhang, B, Leib, SR, Littke, MH and McGuire, TC (2003). Moderate to high avidity Rev-specific memory cytotoxic T lymphocytes correlate with control of viral load and clinical disease in horses with equine infectious anemia virus. Virology 313: 537–552.CrossRefGoogle Scholar
Montelaro, RC, Parekh, B, Orrego, A and Issel, CJ (1984). Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus. Journal of Biological Chemistry 259: 10539–10544.CrossRefGoogle ScholarPubMed
Ogg, GS, Jin, X, Bonhoeffer, S, Dunbar, PR, Nowak, MA, Monard, S, Segal, JP, Cao, Y, Rowland-Jones, SL, Cerundolo, V, Hurley, A, Markowitz, M, Ho, DD, Nixon, DF and McMichael, AJ (1998). Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma viral RNA load. Science 279: 2103–2106.CrossRefGoogle Scholar
Ourmanov, I, Brown, CR, Moss, B, Carroll, M, Wyatt, L, Pletneva, L, Goldstein, S, Venzon, D and Hirsch, VM (2000). Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV. Journal of Virology 74: 2740–2751.CrossRefGoogle ScholarPubMed
Perryman, LE, O'Rourke, KI and McGuire, TC (1988). Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. Journal of Virology 62: 3073–3076.CrossRefGoogle ScholarPubMed
Ridgely, SL and McGuire, TC (2002). Lipopeptide stimulation of MHC class I-restricted memory cytotoxic T lymphocytes from equine infectious anemia virus-infected horses. Vaccine 20: 1809–1819.CrossRefGoogle ScholarPubMed
Ridgely, SL, Zhang, B and McGuire, TC (2003). Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge. Vaccine 21: 491–506.CrossRefGoogle ScholarPubMed
Schmitz, JE, Kuroda, MJ, Santra, S, Sasseville, VG, Simon, MA, Lifton, MA, Racz, P, Tenner-Racz, K, Dalesandro, M, Scallon, BJ, Ghrayeb, J, Forman, MA, Montefiori, DC, Rieber, EP, Letvin, NL and Reimann, KA (1999). Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283: 857–860.CrossRefGoogle ScholarPubMed
Wilson, JD, Ogg, GS, Allen, RL, Davis, C, Shaunak, S, Downie, J, Dyer, W, Workman, C, Sullivan, S, McMichael, AJ, Rowland-Jones, SL (2000). Direct visualization of HIV-1-specific cytotoxic T lymphocytes during primary infection. AIDS 14: 225–233.CrossRefGoogle ScholarPubMed
Yasutomi, Y, Reimann, KA, Lord, CI, Miller, MD and Letvin, NL (1993). Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys. Journal of Virology 67: 1707–1711.CrossRefGoogle ScholarPubMed
Zhang, W, Lonning, SM, McGuire, TC. (1998). Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection. Journal of Virology 72: 9612–9620.CrossRefGoogle ScholarPubMed