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Virology1997; 238(1); 85-93; doi: 10.1006/viro.1997.8795

Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses.

Abstract: Horses with equine infectious anemia virus (EIAV) have episodes of viremia and disease; however, most eventually become inapparent carriers. A possible mechanism of control is cytotoxic T lymphocytes (CTL). To evaluate CTL in inapparent carriers with low viral loads, peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous EIAV-infected PBMC and human IL-2 to detect memory CTL (CTLm). In initial studies, three carriers had CTLm and one of these had low-level effector CTL (CTLe). The CTLm were restricted by equine lymphocyte alloantigen-A (ELA-A) locus encoded MHC class I molecules on autologous equine kidney (EK) target cells. In addition, EK cells did not express MHC class II molecules. The CTLm frequency in PBMC from five inapparent carriers infected for 22 to 50 months was determined by limiting dilution analysis. PBMC were diluted, stimulated, and tested on EK cell targets infected with EIAV and recombinant vaccinia viruses expressing EIAV Env or Gag/Pr proteins. All five carriers had CTLm to EIAV-infected targets, while four had CTLm to targets expressing Env and four had CTLm to targets expressing Gag/Pr proteins. The CTLm frequency range was 60 to 468 per 10(6) PBMC to EIAV-infected targets, 4 to 286 to Env-expressing targets, and 25 to 190 to Gag/Pr-expressing targets. These results should facilitate the identification of epitopes recognized by predominant CTLm from horses controlling a lentivirus infection.
Publication Date: 1997-12-31 PubMed ID: 9375012DOI: 10.1006/viro.1997.8795Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

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 research explores how horses with Equine Infectious Anemia Virus (EIAV) might keep the disease in check due to cytotoxic T lymphocytes (CTL), particularly memory CTL. Researchers specifically investigate CTL in carriers with low viral loads and analyze how they respond to the EIAV virus proteins.

Methodology and Initial Findings

The study began by igniting in vitro stimulation of peripheral blood mononuclear cells (PBMC) from four carrier horses with autologous EIAV-infected PBMC and human IL-2. The aim was to determine the presence and frequency of memory cytotoxic T lymphocytes (CTLm), which are believed to ‘remember’ pathogens and viruses. Three out of four horses had detectable CTLm; one of them also had low-level effector CTL (CTLe).

The CTLm were restricted by equine lymphocyte alloantigen-A (ELA-A) locus-encoded MHC class I molecules found on autologous equine kidney (EK) target cells, signifying a specific immune response to the virus. Notably, the researchers found no expression of MHC class II molecules on EK cells.

Evaluation of CTLm Frequency in Inapparent Carriers

Subsequent steps involved determining the frequency of CTLm in PBMC from five carrier horses that had been infected with EIAV for 22 to 50 months. The team achieved this by using limiting dilution analysis.

  • The researchers collected the PBMC, diluted, and stimulated them.
  • They tested the stimulated PBMC on EK cell targets that were infected with EIAV and recombinant vaccinia viruses expressing EIAV Env or Gag/Pr proteins.

Outcomes

All five horses had demonstrable CTLm in response to EIAV-infected targets. Four out of five horses demonstrated CTLm reaction to the targets expressing the EIAV Env protein and four horses also showed CTLm response to Gag/Pr-expressing targets. The frequency of CTLm ranged from 60 to 468 per million PBMC for the EIAV-infected targets, 4 to 286 for the Env-expressing targets, and 25 to 190 for the Gag/Pr-expressing targets.

Implications of the Study

These results could provide significant insights that may facilitate the identification of epitopes recognized by dominant CTLm from horses controlling lentivirus infection that can serve as potential vaccines or therapeutic targets for EIAV.

Cite This Article

APA
McGuire TC, Zhang W, Hines MT, Henney PJ, Byrne KM. (1997). Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses. Virology, 238(1), 85-93. https://doi.org/10.1006/viro.1997.8795

Publication

ISSN: 0042-6822
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 238
Issue: 1
Pages: 85-93

Researcher Affiliations

McGuire, T C
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA. mcguiret@vetmed.wsu.edu
Zhang, W
    Hines, M T
      Henney, P J
        Byrne, K M

          MeSH Terms

          • Animals
          • Carrier State / immunology
          • Carrier State / veterinary
          • Carrier State / virology
          • Cells, Cultured
          • Cytotoxicity, Immunologic
          • Equine Infectious Anemia / immunology
          • Haplotypes
          • Horses / immunology
          • Horses / virology
          • Humans
          • Immunologic Memory
          • Infectious Anemia Virus, Equine / immunology
          • Interleukin-2 / pharmacology
          • Kidney / immunology
          • Kidney / virology
          • Lymphocyte Activation
          • Lymphocyte Count
          • Lymphocytes / immunology
          • Lymphocytes / virology
          • T-Lymphocytes, Cytotoxic / drug effects
          • T-Lymphocytes, Cytotoxic / immunology
          • Time Factors
          • Viral Proteins / immunology

          Grant Funding

          • AI-24291 / NIAID NIH HHS

          Citations

          This article has been cited 7 times.
          1. 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
          2. Mealey RH, Lee JH, Leib SR, Littke MH, McGuire TC. A single amino acid difference within the alpha-2 domain of two naturally occurring equine MHC class I molecules alters the recognition of Gag and Rev epitopes by equine infectious anemia virus-specific CTL.. J Immunol 2006 Nov 15;177(10):7377-90.
            doi: 10.4049/jimmunol.177.10.7377pubmed: 17082657google scholar: lookup
          3. Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR, McGuire TC. Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes.. Virology 2005 Aug 15;339(1):110-26.
            doi: 10.1016/j.virol.2005.05.025pubmed: 15979679google scholar: lookup
          4. Mealey RH, Zhang B, Leib SR, Littke MH, McGuire TC. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus.. Virology 2003 Sep 1;313(2):537-52.
            doi: 10.1016/s0042-6822(03)00344-1pubmed: 12954220google scholar: lookup
          5. Mealey RH, Fraser DG, Oaks JL, Cantor GH, McGuire TC. Immune reconstitution prevents continuous equine infectious anemia virus replication in an Arabian foal with severe combined immunodeficiency: lessons for control of lentiviruses.. Clin Immunol 2001 Nov;101(2):237-47.
            doi: 10.1006/clim.2001.5109pubmed: 11683583google scholar: lookup
          6. Lonning SM, Zhang W, Leib SR, McGuire TC. Detection and induction of equine infectious anemia virus-specific cytotoxic T-lymphocyte responses by use of recombinant retroviral vectors.. J Virol 1999 Apr;73(4):2762-9.
          7. 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.