The Role of In Vitro-Induced Lymphocyte Apoptosis in Feline Immunodeficiency Virus Infection: Correlation with Different Markers of Disease Progression

  1. Hans Lutz1,*
  1. Clinical Laboratory, Department of Internal Veterinary Medicine,1 and
  2. Swiss National Center for Retroviruses,6 University of Zurich,
  3. Institute of Biomedical Engineering, Swiss Institute of Technology,3 and
  4. Laboratory of Clinical Immunology, Department of Internal Medicine, University Hospital,4 Zurich, and
  5. Division of Experimental Pathology, Institute of Animal Pathology, University of Bern, Bern,2 Switzerland, and
  6. 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.
  • * 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.

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