Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins.
Abstract: Cytotoxic T lymphocytes (CTL) can control some viral infections and may be important in the control of lentiviruses, including human immunodeficiency virus type 1. Since there is limited evidence for an in vivo role of CTL in control of lentiviruses, dissection of immune mechanisms in animal lentiviral infections may provide needed information. Horses infected with equine infectious anemia virus (EIAV) a lentivirus, have acute plasma viremia which is terminated in immunocompetent horses. Viremic episodes may recur, but most horses ultimately control infection and become asymptomatic carriers. To begin dissection of the immune mechanisms involved in EIAV control, peripheral blood mononuclear cells (PBMC) from infected horses were evaluated for CTL to EIAV-infected cells. By using noninfected and EIAV-infected autologous equine kidney (EK) cells in 51Cr-release assays, EIAV-specific cytotoxic activity was detected in unstimulated PBMC from three infected horses. The EIAV-specific cytotoxic activity was major histocompatibility complex (MHC) restricted, as determined by assaying EIAV-infected heterologous EK targets, and was mediated by CD8+ T lymphocytes, as determined by depleting these cells by a panning procedure with an anti-CD8 monoclonal antibody. MHC-restricted CD8+ CTL in unstimulated PBMC from infected horses caused significant specific lysis of autologous EK cells infected with recombinant vaccinia viruses expressing EIAV genes, either env or gag plus 5' pol. The EIAV-specific MHC-restricted CD8+ CTL were detected in two EIAV-infected horses within a few days after plasma viremia occurred and were present after viremia was terminated. The detection of these immune effector cells in EIAV-infected horses permits further studies to determine their in vivo role.
Publication Date: 1994-03-01 PubMed ID: 8107209PubMed Central: PMC236601DOI: 10.1128/JVI.68.3.1459-1467.1994Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research investigates the role of cytotoxic T lymphocytes (CTL) from horses infected with equine infectious anemia virus (EIAV) not only in the termination of plasma viremia but also in recognizing Env and Gag/PR proteins, highlighting the importance of these immune cells and pointing towards future studies to ascertain their in vivo role.
Background
- The study is centered around cytotoxic T lymphocytes (CTLs) and their effect on viral infections, particularly lentiviruses like human immunodeficiency virus type 1 and equine infectious anemia virus (EIAV).
- CTLs present a critical immune reaction against viruses, and the researchers are specifically looking at horses infected with EIAV, a type of lentivirus.
- Horses infected with EIAV experience acute plasma viremia which is terminated In immunocompetent horses. Recurring viremic episodes may occur, but generally, horses control the infection and become asymptomatic carriers.
Methodology
- To analyze the immune mechanisms involved in EIAV control, the peripheral blood mononuclear cells (PBMC) from infected horses were evaluated for CTL to EIAV-infected cells.
- Equine kidney (EK) cells, both infected and non-infected with EIAV, were involved in 51Cr-release assays identifying EIAV-specific cytotoxic activity in the PBMC of these horses.
- Determining whether these immune responses were major histocompatibility complex (MHC) restricted involved the use of EIAV-infected heterologous EK targets, and resulted in the response being mediated by CD8+ T lymphocytes.
- Testing on the cells was done using an anti-CD8 monoclonal antibody to remove any CD8+ T lymphocytes, confirming that these cells are central to the EIAV-specific cytotoxic activity.
Findings
- MHC-restricted CD8+ CTLs were found to specifically cause the lysis (destruction) of autologous EK cells infected with recombinant vaccinia viruses that were expressing EIAV genes, either env or gag plus 5′ pol.
- EIAV-specific MHC-restricted CD8+ CTLs could be detected within a few days after the onset of plasma viremia, and continued to be present even after viremia was terminated.
Implications and Future research
- The research proves the existence of these immune effector cells in EIAV-infected horses and opens the door for further in-depth studies to determine their exact role in vivo (within the living organism).
Cite This Article
APA
McGuire TC, Tumas DB, Byrne KM, Hines MT, Leib SR, Brassfield AL, O'Rourke KI, Perryman LE.
(1994).
Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins.
J Virol, 68(3), 1459-1467.
https://doi.org/10.1128/JVI.68.3.1459-1467.1994 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040.
MeSH Terms
- Animals
- CD8 Antigens / immunology
- Equine Infectious Anemia / immunology
- Gene Products, env / genetics
- Gene Products, env / immunology
- Gene Products, gag / immunology
- Histocompatibility Antigens / immunology
- Horses
- Male
- Molecular Sequence Data
- Recombinant Proteins / immunology
- T-Lymphocyte Subsets / immunology
- T-Lymphocytes, Cytotoxic / immunology
- Vaccinia virus / genetics
Grant Funding
- AI24291 / NIAID NIH HHS
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