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.
Clinical Laboratory, Department of Internal Veterinary Medicine, University of Zurich, Zurich, Switzerland.
E
E
Holznagel
R
R
Hofmann-Lehmann
C M
CM
Leutenegger
K
K
Allenspach
S
S
Huettner
U
U
Forster
E
E
Niederer
H
H
Joller
B J
BJ
Willett
U
U
Hummel
G L
GL
Rossi
J
J
Schüpbach
H
H
Lutz
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