Abstract
FIV is a lentivirus infection of cats which induces an immunodeficiency syndrome associated with early qualitative defects in antigen-specific T cell function and with late quantitative defects in CD4+ T lymphocytes. We have observed that peripheral blood mononuclear cells (PBMC) from FIV-infected cats have impaired survival in culture. The mechanism of this in vitro dysfunction and depletion is not known. We have proposed that inappropriate induction of programmed cell death (apoptosis) could account for these in vitro defects. Here, we report that PBMC from FIV-infected cats, with impaired T cell blastogenesis and impaired survival in vitro, undergo an active cell death upon culture, which has the morphological and biochemical characteristics of programmed cell death (PCD). Apoptosis occurred in all six asymptomatic FIV-infected cats, and in none of the nine uninfected cats, which were studied. Changes in cell morphology under both light and electron microscopy, and fragmentation of genomic DNA were characteristic for apoptosing cells. Cell death was spontaneous and occurred in the absence of any stimuli, and culture with the T cell mitogen, concanavalin A (Con A), did not significantly enhance cell death. Activation-induced cell death was inhibited, in a dose-dependent manner, by addition to the incubation medium of zinc, which has been shown to inhibit the action of endonuclease responsible for the characteristic fragmentation of DNA. Since apoptosis has recently been implicated in AIDS pathogenesis, FIV infection may prove useful to study this aspect of retroviral, in particular HIV, infection.
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- Banda N. K., Bernier J., Kurahara D. K., Kurrle R., Haigwood N., Sekaly R. P., Finkel T. H. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J Exp Med. 1992 Oct 1;176(4):1099–1106. doi: 10.1084/jem.176.4.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barlough J. E., Ackley C. D., George J. W., Levy N., Acevedo R., Moore P. F., Rideout B. A., Cooper M. D., Pedersen N. C. Acquired immune dysfunction in cats with experimentally induced feline immunodeficiency virus infection: comparison of short-term and long-term infections. J Acquir Immune Defic Syndr. 1991;4(3):219–227. [PubMed] [Google Scholar]
- Bishop S. A., Williams N. A., Gruffydd-Jones T. J., Harbour D. A., Stokes C. R. An early defect in primary and secondary T cell responses in asymptomatic cats during acute feline immunodeficiency virus (FIV) infection. Clin Exp Immunol. 1992 Dec;90(3):491–496. doi: 10.1111/j.1365-2249.1992.tb05872.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bishop S. A., Williams N. A., Gruffydd-Jones T. J., Harbour D. A., Stokes C. R. Impaired T-cell priming and proliferation in cats infected with feline immunodeficiency virus. AIDS. 1992 Mar;6(3):287–293. doi: 10.1097/00002030-199203000-00005. [DOI] [PubMed] [Google Scholar]
- Blackman M., Kappler J., Marrack P. The role of the T cell receptor in positive and negative selection of developing T cells. Science. 1990 Jun 15;248(4961):1335–1341. doi: 10.1126/science.1972592. [DOI] [PubMed] [Google Scholar]
- Brown W. C., Bissey L., Logan K. S., Pedersen N. C., Elder J. H., Collisson E. W. Feline immunodeficiency virus infects both CD4+ and CD8+ T lymphocytes. J Virol. 1991 Jun;65(6):3359–3364. doi: 10.1128/jvi.65.6.3359-3364.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunner D., Pedersen N. C. Infection of peritoneal macrophages in vitro and in vivo with feline immunodeficiency virus. J Virol. 1989 Dec;63(12):5483–5488. doi: 10.1128/jvi.63.12.5483-5488.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cayota A., Vuillier F., Scott-Algara D., Feuillie V., Dighiero G. Impaired proliferative capacity and abnormal cytokine profile of naive and memory CD4 T cells from HIV-seropositive patients. Clin Exp Immunol. 1992 Jun;88(3):478–483. doi: 10.1111/j.1365-2249.1992.tb06475.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen J. J., Duke R. C. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol. 1984 Jan;132(1):38–42. [PubMed] [Google Scholar]
- Dow S. W., Poss M. L., Hoover E. A. Feline immunodeficiency virus: a neurotropic lentivirus. J Acquir Immune Defic Syndr. 1990;3(7):658–668. [PubMed] [Google Scholar]
- Duke R. C., Chervenak R., Cohen J. J. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6361–6365. doi: 10.1073/pnas.80.20.6361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groux H., Torpier G., Monté D., Mouton Y., Capron A., Ameisen J. C. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med. 1992 Feb 1;175(2):331–340. doi: 10.1084/jem.175.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hopper C. D., Sparkes A. H., Gruffydd-Jones T. J., Crispin S. M., Muir P., Harbour D. A., Stokes C. R. Clinical and laboratory findings in cats infected with feline immunodeficiency virus. Vet Rec. 1989 Sep 23;125(13):341–346. doi: 10.1136/vr.125.13.341. [DOI] [PubMed] [Google Scholar]
- Hosie M. J., Willett B. J., Dunsford T. H., Jarrett O., Neil J. C. A monoclonal antibody which blocks infection with feline immunodeficiency virus identifies a possible non-CD4 receptor. J Virol. 1993 Mar;67(3):1667–1671. doi: 10.1128/jvi.67.3.1667-1671.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDonald H. R., Lees R. K. Programmed death of autoreactive thymocytes. Nature. 1990 Feb 15;343(6259):642–644. doi: 10.1038/343642a0. [DOI] [PubMed] [Google Scholar]
- Martin S. J., Cotter T. G. Ultraviolet B irradiation of human leukaemia HL-60 cells in vitro induces apoptosis. Int J Radiat Biol. 1991 Apr;59(4):1001–1016. doi: 10.1080/09553009114550891. [DOI] [PubMed] [Google Scholar]
- Meyaard L., Otto S. A., Jonker R. R., Mijnster M. J., Keet R. P., Miedema F. Programmed death of T cells in HIV-1 infection. Science. 1992 Jul 10;257(5067):217–219. doi: 10.1126/science.1352911. [DOI] [PubMed] [Google Scholar]
- Pedersen N. C., Ho E. W., Brown M. L., Yamamoto J. K. Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science. 1987 Feb 13;235(4790):790–793. doi: 10.1126/science.3643650. [DOI] [PubMed] [Google Scholar]
- Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]
- Wyllie A. H., Morris R. G., Smith A. L., Dunlop D. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol. 1984 Jan;142(1):67–77. doi: 10.1002/path.1711420112. [DOI] [PubMed] [Google Scholar]
- Yamamoto J. K., Sparger E., Ho E. W., Andersen P. R., O'Connor T. P., Mandell C. P., Lowenstine L., Munn R., Pedersen N. C. Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats. Am J Vet Res. 1988 Aug;49(8):1246–1258. [PubMed] [Google Scholar]
- Yamamoto J. K., Sparger E., Ho E. W., Andersen P. R., O'Connor T. P., Mandell C. P., Lowenstine L., Munn R., Pedersen N. C. Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats. Am J Vet Res. 1988 Aug;49(8):1246–1258. [PubMed] [Google Scholar]



