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Enhanced expression of novel CD57+CD8+ LAK cells from cats infected with feline immunodeficiency virus
1Department of Microbiology, Pathology and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh 27695-8401, USA.
Insights
Feline immunodeficiency virus (FIV) infection enhances lymphokine-activated killer (LAK) cell function in cats. These CD8+CD57+ LAK cells may contribute to the prolonged asymptomatic phase observed in FIV-infected individuals.
Area of Science:
- Immunology
- Virology
- Comparative Medicine
Background:
- Feline immunodeficiency virus (FIV) infection in cats serves as a model for human immunodeficiency virus (HIV) infection.
- Lymphokine-activated killer (LAK) cell function is crucial in immune responses but can be impaired in immunodeficiency.
- Understanding LAK cell behavior in FIV infection can provide insights into immune dysregulation during lentiviral infections.
Purpose of the Study:
- To investigate the function and phenotype of LAK cells in cats infected with FIV.
- To compare LAK cell cytotoxicity between FIV-infected and uninfected cats.
- To identify the specific cell populations responsible for LAK activity in FIV infection.
Main Methods:
- Peripheral blood mononuclear cells from FIV-infected and control cats were cultured with concanavalin A and interleukin-2 to induce LAK cells.
- LAK cell cytotoxicity was assessed against chronically FIV-infected cells, acutely infected lymphocytes, and feline leukemia virus-infected cells.
- Two-color fluorescence-activated cell sorter analysis and antibody depletion were used to characterize LAK cell surface markers, specifically CD8 and CD57.
Main Results:
- LAK cells from FIV-infected cats exhibited enhanced cytotoxicity against both FIV-infected and feline leukemia virus-infected cells compared to LAK cells from uninfected cats.
- The enhanced cytotoxicity was not antigen-specific.
- The majority of induced LAK cells and their progenitors in FIV-infected cats were identified as CD8+CD57+ cells, and their in vitro induction was increased.
Conclusions:
- FIV infection enhances LAK cell-mediated cytotoxicity in cats.
- The CD8+CD57+ LAK cell population is significantly expanded and functionally enhanced in FIV-infected cats.
- These findings suggest that CD8+CD57+ LAK cells may play a role in the prolonged asymptomatic stage of FIV infection, potentially through non-specific cytotoxic mechanisms.
Abstract:
As a model for lymphokine-activated killer (LAK) function in HIV infection, we studied LAK cells in cats infected with feline immunodeficiency virus (FIV), which causes an acquired immunodeficiency syndrome. Peripheral blood mononuclear cells cultured in concanavalin A and interleukin-2 developed LAK cytotoxicity against chronically FIV-infected CrFK cells and acutely infected CD4+ lymphocytes but not uninfected cells. LAK cells from FIV+ cats were more cytotoxic than LAK cells from uninfected cats. Enhanced FIV+ LAK cytotoxicity against feline leukemia virus-infected cells (FL74) suggested that the cytotoxicity was not antigen specific. Two-color fluorescence-activated cell sorter analysis and antibody depletion studies demonstrated that the majority of LAK cells and their progenitors were positive for both CD8 and CD57. The in vitro induction of dual positive CD8+CD57+ LAK cells was enhanced in FIV+ cats, as reported for HIV+ patients. These CD8+CD57+ LAK cells may play a role in maintaining the long asymptomatic stage of infection in FIV+ cats.