The role of in vitro-induced lymphocyte apoptosis in feline immunodeficiency virus infection: correlation with different markers of disease progression.
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.
Holznagel
E
E
Clinical Laboratory, Department of Internal Veterinary Medicine, University of Zurich, Zurich, Switzerland.
Hofmann-Lehmann
R
R
Leutenegger
C M
CM
Allenspach
K
K
Huettner
S
S
Forster
U
U
Niederer
E
E
Joller
H
H
Willett
B J
BJ
Hummel
U
U
Rossi
G L
GL
Schüpbach
J
J
Lutz
H
H
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D005260:Female; D015683:Gene Products, gag / Q000032:analysis; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000276:immunology / Q000472:pathogenicity*; D066298:In Vitro Techniques; D016180:Lentivirus Infections / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D015683:Gene Products, gag; D014409:Tumor Necrosis Factor-alpha; C074662:p24 protein, Feline immunodeficiency virus