Abstract
Mice of the SJL/J and BALB/cByJ inbred strains are naturally resistant to street rabies virus (SRV) injected via the intraperitoneal route. To determine the cellular mechanism of resistance, monoclonal antibodies specific for CD4+ or CD8+ subsets of T cells were used to deplete the respective cell population in SRV-infected animals. Elimination of CD4+ T-helper cells abrogated the production of immunoglobulin G (IgG) neutralizing antibodies in response to rabies virus infection and reversed the resistant status of SJL/J and BALB/cByJ mice. In contrast, in vivo depletion of CD8+ cytotoxic T cells had no measurable effect on host resistance to SRV. These results indicate that serum neutralizing antibodies of the IgG class are a primary immunological mechanism of defense against rabies virus infection in this murine model of disease. CD8+ cytotoxic T lymphocytes, which have been shown to transfer protection in other rabies virus systems, appear to have no role in protecting mice against intraperitoneally injected SRV.
Full text
PDF![3429](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b31/241322/480d9e6125db/jvirol00050-0025.png)
![3430](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b31/241322/aeb5787e3f44/jvirol00050-0026.png)
![3431](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b31/241322/3a7ced151715/jvirol00050-0027.png)
![3432](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b31/241322/0b7d526e7f14/jvirol00050-0028.png)
![3433](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b31/241322/83502a184339/jvirol00050-0029.png)
![3434](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b31/241322/aec647e7554c/jvirol00050-0030.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andrew M. E., Coupar B. E., Boyle D. B., Ada G. L. The roles of influenza virus haemagglutinin and nucleoprotein in protection: analysis using vaccinia virus recombinants. Scand J Immunol. 1987 Jan;25(1):21–28. doi: 10.1111/j.1365-3083.1987.tb01042.x. [DOI] [PubMed] [Google Scholar]
- BAILEY D. W. Histoincompatibility associated with the X chromosome in mice. Transplantation. 1963 Jan;1:70–74. doi: 10.1097/00007890-196301010-00009. [DOI] [PubMed] [Google Scholar]
- Bunschoten H., Gore M., Claassen I. J., Uytdehaag F. G., Dietzschold B., Wunner W. H., Osterhaus A. D. Characterization of a new virus-neutralizing epitope that denotes a sequential determinant on the rabies virus glycoprotein. J Gen Virol. 1989 Feb;70(Pt 2):291–298. doi: 10.1099/0022-1317-70-2-291. [DOI] [PubMed] [Google Scholar]
- Celis E., Ou D., Dietzschold B., Koprowski H. Recognition of rabies and rabies-related viruses by T cells derived from human vaccine recipients. J Virol. 1988 Sep;62(9):3128–3134. doi: 10.1128/jvi.62.9.3128-3134.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cho S., Narahara H., Mifune K., Kawai A. Murine T cell clones directed to rabies virus: isolation and some of their properties. J Gen Virol. 1987 Apr;68(Pt 4):1115–1123. doi: 10.1099/0022-1317-68-4-1115. [DOI] [PubMed] [Google Scholar]
- Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. doi: 10.1038/312548a0. [DOI] [PubMed] [Google Scholar]
- Cox J. H., Dietzschold B., Schneider L. G. Rabies virus glycoprotein. II. Biological and serological characterization. Infect Immun. 1977 Jun;16(3):754–759. doi: 10.1128/iai.16.3.754-759.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dietzschold B., Wang H. H., Rupprecht C. E., Celis E., Tollis M., Ertl H., Heber-Katz E., Koprowski H. Induction of protective immunity against rabies by immunization with rabies virus ribonucleoprotein. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9165–9169. doi: 10.1073/pnas.84.24.9165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ertl H. C., Dietzschold B., Gore M., Otvos L., Jr, Larson J. K., Wunner W. H., Koprowski H. Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein. J Virol. 1989 Jul;63(7):2885–2892. doi: 10.1128/jvi.63.7.2885-2892.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Esposito J., Brechling K., Baer G., Moss B. Vaccinia virus recombinants expressing rabiesvirus glycoprotein protect against rabies. Virus Genes. 1987 Nov;1(1):7–21. doi: 10.1007/BF00125682. [DOI] [PubMed] [Google Scholar]
- Flynn J. C., Conaway D. H., Cobbold S., Waldmann H., Kong Y. C. Depletion of L3T4+ and Lyt-2+ cells by rat monoclonal antibodies alters the development of adoptively transferred experimental autoimmune thyroiditis. Cell Immunol. 1989 Sep;122(2):377–390. doi: 10.1016/0008-8749(89)90085-3. [DOI] [PubMed] [Google Scholar]
- Kawano H., Mifune K., Ohuchi M., Mannen K., Cho S., Hiramatsu K., Shichijo A. Protection against rabies in mice by a cytotoxic T cell clone recognizing the glycoprotein of rabies virus. J Gen Virol. 1990 Feb;71(Pt 2):281–287. doi: 10.1099/0022-1317-71-2-281. [DOI] [PubMed] [Google Scholar]
- Kong Y. M., Giraldo A. A., Waldmann H., Cobbold S. P., Fuller B. E. Resistance to experimental autoimmune thyroiditis: L3T4+ cells as mediators of both thyroglobulin-activated and TSH-induced suppression. Clin Immunol Immunopathol. 1989 Apr;51(1):38–54. doi: 10.1016/0090-1229(89)90204-3. [DOI] [PubMed] [Google Scholar]
- Lafon M., Wiktor T. J., Macfarlan R. I. Antigenic sites on the CVS rabies virus glycoprotein: analysis with monoclonal antibodies. J Gen Virol. 1983 Apr;64(Pt 4):843–851. doi: 10.1099/0022-1317-64-4-843. [DOI] [PubMed] [Google Scholar]
- Lagrange P. H., Tsiang H., Hurtrel B., Ravisse P. Delayed-type hypersensitivity to rabies virus in mice: assay of active or passive sensitization by the footpad test. Infect Immun. 1978 Sep;21(3):931–939. doi: 10.1128/iai.21.3.931-939.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lodmell D. L., Arai Y. T., Ewalt L. C. Influence of cell type and virus upon lysis of rabies virus-infected cells by antibody and complement. Arch Virol. 1981;70(2):147–155. doi: 10.1007/BF01315008. [DOI] [PubMed] [Google Scholar]
- Lodmell D. L., Bell J. F., Moore G. J., Raymond G. H. Comparative study of abortive and nonabortive rabies in mice. J Infect Dis. 1969 Jun;119(6):569–580. doi: 10.1093/infdis/119.6.569. [DOI] [PubMed] [Google Scholar]
- Lodmell D. L., Ewalt L. C. Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice. J Virol. 1985 Sep;55(3):788–795. doi: 10.1128/jvi.55.3.788-795.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lodmell D. L. Genetic control of resistance to street rabies virus in mice. J Exp Med. 1983 Feb 1;157(2):451–460. doi: 10.1084/jem.157.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lodmell D. L., Wiedbrauk D. L., Ewalt L. C. Interferon induced within the central nervous system during infection is inconsequential as a mechanism responsible for murine resistance to street rabies virus. J Gen Virol. 1989 Feb;70(Pt 2):473–478. doi: 10.1099/0022-1317-70-2-473. [DOI] [PubMed] [Google Scholar]
- Maraskovsky E., Chen W. F., Shortman K. IL-2 and IFN-gamma are two necessary lymphokines in the development of cytolytic T cells. J Immunol. 1989 Aug 15;143(4):1210–1214. [PubMed] [Google Scholar]
- Miller A., Morse H. C., 3rd, Winkelstein J., Nathanson N. The role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells. J Immunol. 1978 Jul;121(1):321–326. [PubMed] [Google Scholar]
- Nash A. A., Jayasuriya A., Phelan J., Cobbold S. P., Waldmann H., Prospero T. Different roles for L3T4+ and Lyt 2+ T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system. J Gen Virol. 1987 Mar;68(Pt 3):825–833. doi: 10.1099/0022-1317-68-3-825. [DOI] [PubMed] [Google Scholar]
- Nilsson M. R., Sant'anna O. A., Siqueira M., Nilsson T. T., Gennari M. Rabies virus immunity in genetically selected high- and low-responder lines of mice. Infect Immun. 1979 Jul;25(1):23–26. doi: 10.1128/iai.25.1.23-26.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pereira C. A., Nozaki-Renard J. N., Schwartz J., Eyquem A., Atanasiu P. Cytotoxicity reactions against target cells infected with rabies virus. J Virol Methods. 1982 Oct;5(2):75–83. doi: 10.1016/0166-0934(82)90084-2. [DOI] [PubMed] [Google Scholar]
- Perrin P., Joffret M. L., Leclerc C., Oth D., Sureau P., Thibodeau L. Interleukin 2 increases protection against experimental rabies. Immunobiology. 1988 May;177(2):199–209. doi: 10.1016/S0171-2985(88)80039-1. [DOI] [PubMed] [Google Scholar]
- Perry L. L., Hotchkiss J. D., Lodmell D. L. Murine susceptibility to street rabies virus is unrelated to induction of host lymphoid depletion. J Immunol. 1990 May 1;144(9):3552–3557. [PubMed] [Google Scholar]
- Perry L. L., Williams I. R. Regulation of transplantation immunity in vivo by monoclonal antibodies recognizing host class II restriction elements. I. Genetics and specificity of anti-Ia immunotherapy in murine skin allograft recipients. J Immunol. 1985 May;134(5):2935–2941. [PubMed] [Google Scholar]
- Rodriguez M., Sriram S. Successful therapy of Theiler's virus-induced demyelination (DA strain) with monoclonal anti-Lyt-2 antibody. J Immunol. 1988 May 1;140(9):2950–2955. [PubMed] [Google Scholar]
- Smith J. S., Yager P. A., Baer G. M. A rapid reproducible test for determining rabies neutralizing antibody. Bull World Health Organ. 1973 May;48(5):535–541. [PMC free article] [PubMed] [Google Scholar]
- Sugamata M., Ewalt L. C., Perry L. L., Lodmell D. L. Detection of anti-rabies virus cytotoxic T lymphocytes in mice of four distinct H-2 haplotypes using target cells persistently infected with ERA rabies virus. J Virol Methods. 1990 Jul;29(1):1–11. doi: 10.1016/0166-0934(90)90002-w. [DOI] [PubMed] [Google Scholar]
- Tolson N. D., Charlton K. M., Stewart R. B., Campbell J. B., Wiktor T. J. Immune response in skunks to a vaccinia virus recombinant expressing the rabies virus glycoprotein. Can J Vet Res. 1987 Jul;51(3):363–366. [PMC free article] [PubMed] [Google Scholar]
- Turner G. S. Immunoglobulin (IgG) and (IgM) antibody responses to rabies vaccine. J Gen Virol. 1978 Sep;40(3):595–604. doi: 10.1099/0022-1317-40-3-595. [DOI] [PubMed] [Google Scholar]
- Wiktor T. J., Doherty P. C., Koprowski H. Suppression of cell-mediated immunity by street rabies virus. J Exp Med. 1977 Jun 1;145(6):1617–1622. doi: 10.1084/jem.145.6.1617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiktor T. J., Kuwert E., Koprowski H. Immune lysis of rabies virus-infected cells. J Immunol. 1968 Dec;101(6):1271–1282. [PubMed] [Google Scholar]
- Williams I. R., Perry L. L. A double determinant sandwich immunoassay for quantitation of serum monoclonal anti-I-A antibody. J Immunol Methods. 1985 Dec 27;85(2):279–294. doi: 10.1016/0022-1759(85)90138-3. [DOI] [PubMed] [Google Scholar]