The Role of In Vitro-Induced Lymphocyte Apoptosis in Feline Immunodeficiency Virus Infection: Correlation with Different Markers of Disease Progression
- Edgar Holznagel1,2,
- Regina Hofmann-Lehmann1,
- Christian M. Leutenegger1,
- Karin Allenspach1,
- Silke Huettner1,
- Ursula Forster2,
- Eva Niederer3,
- Helen Joller4,
- Brian J. Willett5,
- Urs Hummel6,
- Giovanni L. Rossi2,
- Jörg Schüpbach6, and
- Hans Lutz1,*
- Clinical Laboratory, Department of Internal Veterinary Medicine,1 and
- Swiss National Center for Retroviruses,6 University of Zurich,
- Institute of Biomedical Engineering, Swiss Institute of Technology,3 and
- Laboratory of Clinical Immunology, Department of Internal Medicine, University Hospital,4 Zurich, and
- Division of Experimental Pathology, Institute of Animal Pathology, University of Bern, Bern,2 Switzerland, and
- Department of Veterinary Pathology, University of Glasgow, Glasgow, United Kingdom5
ABSTRACT
Human immunodeficiency virus infection is characterized by a progressive decline in the number of peripheral blood CD4+T lymphocytes, which finally leads to AIDS. This T-cell decline correlates with the degree of in vitro-induced lymphocyte apoptosis. However, such a correlation has not yet been described in feline AIDS, caused by feline immunodeficiency virus (FIV) infection. We therefore investigated the intensity of in vitro-induced apoptosis in peripheral blood lymphocytes from cats experimentally infected with a Swiss isolate of FIV for 1 year and for 6 years and from a number of long-term FIV-infected cats which were coinfected with feline leukemia virus. Purified peripheral blood lymphocytes were either cultured overnight under nonstimulating conditions or stimulated with phytohemagglutinin and interleukin-2 for 60 h. Under stimulating conditions, the isolates from the infected cats showed significantly higher relative counts of apoptotic cells than did those from noninfected controls (1-year-infected cats, P = 0.01; 6-year-infected cats, P = 0.006). The frequency of in vitro-induced apoptosis was inversely correlated with the CD4+ cell count (P = 0.002), bright CD8+ cell count (P = 0.009), and CD4/CD8 ratio (P = 0.01) and directly correlated with the percentage of bright major histocompatibility complex class II-positive peripheral blood lymphocytes (P = 0.004). However, we found no correlation between in vitro-induced apoptosis and the viral load in serum samples. Coinfection with feline leukemia virus enhanced the degree of in vitro-induced apoptosis compared with that in FIV monoinfected cats. We concluded that the degree of in vitro-induced apoptosis was closely related to FIV-mediated T-cell depletion and lymphocyte activation and could be used as an additional marker for disease progression in FIV infection.
FOOTNOTES
- Received 28 May 1998.
- Accepted 13 July 1998.
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↵* Corresponding author. Mailing address: Clinical Laboratory, Department of Internal Veterinary Medicine, University of Zurich, Wintherthurer Str. 260, CH-8057 Zurich, Switzerland. Phone: 41-1-6358312. Fax: 41-1-6358906. E-mail:hanslutz{at}vetklinik.unizh.ch.
- Copyright © 1998 American Society for Microbiology











