Abstract
Human immunodeficiency virus (HIV) causes a long, asymptomatic infection characterized by normal to elevated numbers of circulating CD8+ cells and a progressive decline in CD4+ cells. It has been speculated that HIV-specific antiviral activity driven by CD8+ T cells may control viral replication during this period and maintain the clinically asymptomatic stage of disease. The disease induced in cats by feline immunodeficiency virus (FIV) is similar to HIV in that it is characterized by a long asymptomatic stage with a progressive decline in CD4+ cells, culminating in AIDS. In the present study, we demonstrate that FIV is more readily isolated from CD8+ T-cell-depleted peripheral blood mononuclear cells (PBMC) of FIV-infected cats than from unfractionated PBMC cultures. In addition, CD8+ T cells isolated from FIV-positive cats demonstrating anti-FIV activity in PBMC cultures inhibit FIV infection of FCD4E cells in vitro. Anti-FIV activity is not found in FIV- negative cats and is not characteristic of cats acutely infected with FIV but is present in the majority of chronically infected, clinically asymptomatic and symptomatic cats. Decreases in plasma and cell-associated viremia during the acute-stage FIV infection appears to precede the appearance of CD8+ anti-FIV cells in the circulation. In summary, this study demonstrates a population(s) of CD8+ T cells in chronically FIV-infected cats capable of suppressing FIV replication in cultured PBMC. The significance of anti-FIV CD8+ cells in the immunopathogenesis of the infection and disease progression has yet to be determined.
Full Text
The Full Text of this article is available as a PDF (232.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Brinchmann J. E., Gaudernack G., Vartdal F. CD8+ T cells inhibit HIV replication in naturally infected CD4+ T cells. Evidence for a soluble inhibitor. J Immunol. 1990 Apr 15;144(8):2961–2966. [PubMed] [Google Scholar]
- Davidson M. G., Rottman J. B., English R. V., Lappin M. R., Tompkins M. B. Feline immunodeficiency virus predisposes cats to acute generalized toxoplasmosis. Am J Pathol. 1993 Nov;143(5):1486–1497. [PMC free article] [PubMed] [Google Scholar]
- Diehl L. J., Mathiason-DuBard C. K., O'Neil L. L., Hoover E. A. Longitudinal assessment of feline immunodeficiency virus kinetics in plasma by use of a quantitative competitive reverse transcriptase PCR. J Virol. 1995 Apr;69(4):2328–2332. doi: 10.1128/jvi.69.4.2328-2332.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- English R. V., Johnson C. M., Gebhard D. H., Tompkins M. B. In vivo lymphocyte tropism of feline immunodeficiency virus. J Virol. 1993 Sep;67(9):5175–5186. doi: 10.1128/jvi.67.9.5175-5186.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- English R. V., Nelson P., Johnson C. M., Nasisse M., Tompkins W. A., Tompkins M. B. Development of clinical disease in cats experimentally infected with feline immunodeficiency virus. J Infect Dis. 1994 Sep;170(3):543–552. doi: 10.1093/infdis/170.3.543. [DOI] [PubMed] [Google Scholar]
- Fauci A. S. Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science. 1993 Nov 12;262(5136):1011–1018. doi: 10.1126/science.8235617. [DOI] [PubMed] [Google Scholar]
- Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
- Gardner M. B. Simian and feline immunodeficiency viruses: animal lentivirus models for evaluation of AIDS vaccines and antiviral agents. Antiviral Res. 1991 May;15(4):267–286. doi: 10.1016/0166-3542(91)90009-g. [DOI] [PubMed] [Google Scholar]
- Goff S., Traktman P., Baltimore D. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase. J Virol. 1981 Apr;38(1):239–248. doi: 10.1128/jvi.38.1.239-248.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
- Kannagi M., Chalifoux L. V., Lord C. I., Letvin N. L. Suppression of simian immunodeficiency virus replication in vitro by CD8+ lymphocytes. J Immunol. 1988 Apr 1;140(7):2237–2242. [PubMed] [Google Scholar]
- Kannagi M., Masuda T., Hattori T., Kanoh T., Nasu K., Yamamoto N., Harada S. Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro. J Virol. 1990 Jul;64(7):3399–3406. doi: 10.1128/jvi.64.7.3399-3406.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackewicz C. E., Ortega H. W., Levy J. A. CD8+ cell anti-HIV activity correlates with the clinical state of the infected individual. J Clin Invest. 1991 Apr;87(4):1462–1466. doi: 10.1172/JCI115153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackewicz C. E., Ortega H., Levy J. A. Effect of cytokines on HIV replication in CD4+ lymphocytes: lack of identity with the CD8+ cell antiviral factor. Cell Immunol. 1994 Feb;153(2):329–343. doi: 10.1006/cimm.1994.1032. [DOI] [PubMed] [Google Scholar]
- Mackewicz C. E., Yang L. C., Lifson J. D., Levy J. A. Non-cytolytic CD8 T-cell anti-HIV responses in primary HIV-1 infection. Lancet. 1994 Dec 17;344(8938):1671–1673. doi: 10.1016/s0140-6736(94)90459-6. [DOI] [PubMed] [Google Scholar]
- Mackewicz C., Levy J. A. CD8+ cell anti-HIV activity: nonlytic suppression of virus replication. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1039–1050. doi: 10.1089/aid.1992.8.1039. [DOI] [PubMed] [Google Scholar]
- North T. W., Cronn R. C., Remington K. M., Tandberg R. T., Judd R. C. Characterization of reverse transcriptase from feline immunodeficiency virus. J Biol Chem. 1990 Mar 25;265(9):5121–5128. [PubMed] [Google Scholar]
- Novotney C., English R. V., Housman J., Davidson M. G., Nasisse M. P., Jeng C. R., Davis W. C., Tompkins M. B. Lymphocyte population changes in cats naturally infected with feline immunodeficiency virus. AIDS. 1990 Dec;4(12):1213–1218. doi: 10.1097/00002030-199012000-00005. [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]
- Powell J. D., Yehuda-Cohen T., Villinger F., McClure H. M., Sell K. W., Ahmed-Ansari A. Inhibition of SIV/SMM replication in vitro by CD8+ cells from SIV/SMM infected seropositive clinically asymptomatic sooty mangabeys. J Med Primatol. 1990;19(3-4):239–249. [PubMed] [Google Scholar]
- Rottman J. B., Freeman E. B., Tonkonogy S., Tompkins M. B. A reverse transcription-polymerase chain reaction technique to detect feline cytokine genes. Vet Immunol Immunopathol. 1995 Mar;45(1-2):1–18. doi: 10.1016/0165-2427(94)05324-l. [DOI] [PubMed] [Google Scholar]
- Tompkins M. B., Gebhard D. H., Bingham H. R., Hamilton M. J., Davis W. C., Tompkins W. A. Characterization of monoclonal antibodies to feline T lymphocytes and their use in the analysis of lymphocyte tissue distribution in the cat. Vet Immunol Immunopathol. 1990 Dec;26(4):305–317. doi: 10.1016/0165-2427(90)90115-9. [DOI] [PubMed] [Google Scholar]
- Tompkins M. B., Nelson P. D., English R. V., Novotney C. Early events in the immunopathogenesis of feline retrovirus infections. J Am Vet Med Assoc. 1991 Nov 15;199(10):1311–1315. [PubMed] [Google Scholar]
- Tompkins M. B., Ogilvie G. K., Franklin R. A., Kelley K. W., Tompkins W. A. Induction of IL-2 and lymphokine activated killer cells in the cat. Vet Immunol Immunopathol. 1987 Sep;16(1-2):1–10. doi: 10.1016/0165-2427(87)90169-3. [DOI] [PubMed] [Google Scholar]
- Torten M., Franchini M., Barlough J. E., George J. W., Mozes E., Lutz H., Pedersen N. C. Progressive immune dysfunction in cats experimentally infected with feline immunodeficiency virus. J Virol. 1991 May;65(5):2225–2230. doi: 10.1128/jvi.65.5.2225-2230.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker C. M., Erickson A. L., Hsueh F. C., Levy J. A. Inhibition of human immunodeficiency virus replication in acutely infected CD4+ cells by CD8+ cells involves a noncytotoxic mechanism. J Virol. 1991 Nov;65(11):5921–5927. doi: 10.1128/jvi.65.11.5921-5927.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker C. M., Levy J. A. A diffusible lymphokine produced by CD8+ T lymphocytes suppresses HIV replication. Immunology. 1989 Apr;66(4):628–630. [PMC free article] [PubMed] [Google Scholar]
- Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
- Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [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]
- Zhao Y., Gebhard D., English R., Sellon R., Tompkins M., Tompkins W. Enhanced expression of novel CD57+CD8+ LAK cells from cats infected with feline immunodeficiency virus. J Leukoc Biol. 1995 Oct;58(4):423–431. doi: 10.1002/jlb.58.4.423. [DOI] [PubMed] [Google Scholar]