Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses.
- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
- Cytokines
- Diagnosis
- Disease control
- Disease Diagnosis
- Equine Diseases
- Equine Health
- Equine Infectious Anemia
- Genetics
- Horses
- Immune Response
- Immunology
- In Vitro Research
- Infection
- Infectious Disease
- Major Histocompatibility Complex (MHC)
- Mononuclear Cells
- T Cells
- Veterinary Medicine
- Veterinary Research
- Virus
- White Blood Cells
Summary
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
Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA. mcguiret@vetmed.wsu.edu
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.- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.