Abstract
Following herpes simplex virus type 1 (HSV-1) infection of the cornea, the virus is transmitted to the trigeminal ganglion, where a brief period of virus replication is followed by establishment of a latent infection in neurons. A possible role of the immune system in regulating virus replication and maintaining latency in the sensory neurons has been suggested. We have investigated the phenotype and cytokine pattern of cells that infiltrate the A/J mouse trigeminal ganglion at various times after HSV-1 corneal infection. HSV antigen expression in the trigeminal ganglion (indicative of the viral lytic cycle) increased until day 3 postinfection (p.i.) and then diminished to undetectable levels by day 7 p.i. The period of declining HSV antigen expression. was associated with a marked increase in Mac-1+ cells. These cells did not appear to coexpress the F4/80+ (macrophage) or the CD8+ (T cell) markers, and none showed polymorphonuclear leukocyte morphology, suggesting a possible early infiltration of natural killer cells. There was also a significant increase in the trigeminal ganglion of cells expressing the gamma delta T-cell receptor, and these cells were found almost exclusively in very close association with neurons. This period was also characterized by a rapid and equivalent increase in cells expressing gamma interferon and interleukin-4. The density of the inflammatory infiltrate in the trigeminal ganglion increased until days 12 to 21 p.i., when it was predominated by CD8+, Mac-1+, and tumor necrosis factor-expressing cells, which surrounded many neurons. By day 92 p.i., the inflammatory infiltrate diminished but was heaviest in mice with active periocular skin disease. Our data are consistent with the notion that gamma interferon produced by natural killer cells and/or gamma delta T cells may play an important role in limiting HSV-1 replication in the trigeminal ganglion during the acute stage of infection. In addition, tumor necrosis factor produced by CD8+ T cells and macrophages may function to maintain the virus in a latent state.
Full Text
The Full Text of this article is available as a PDF (1.8 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arvidson B. Retrograde transport of horseradish peroxidase in sensory and adrenergic neurons following injection into the anterior eye chamber. J Neurocytol. 1979 Dec;8(6):751–764. doi: 10.1007/BF01206674. [DOI] [PubMed] [Google Scholar]
- Bochner B. S., Luscinskas F. W., Gimbrone M. A., Jr, Newman W., Sterbinsky S. A., Derse-Anthony C. P., Klunk D., Schleimer R. P. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med. 1991 Jun 1;173(6):1553–1557. doi: 10.1084/jem.173.6.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doymaz M. Z., Rouse B. T. Herpetic stromal keratitis: an immunopathologic disease mediated by CD4+ T lymphocytes. Invest Ophthalmol Vis Sci. 1992 Jun;33(7):2165–2173. [PubMed] [Google Scholar]
- Feduchi E., Alonso M. A., Carrasco L. Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus. J Virol. 1989 Mar;63(3):1354–1359. doi: 10.1128/jvi.63.3.1354-1359.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feduchi E., Carrasco L. Mechanism of inhibition of HSV-1 replication by tumor necrosis factor and interferon gamma. Virology. 1991 Feb;180(2):822–825. doi: 10.1016/0042-6822(91)90100-p. [DOI] [PubMed] [Google Scholar]
- Granstein R. D., Greene M. I. Splenic I-J-bearing antigen-presenting cells in activation of suppression: further characterization. Cell Immunol. 1985 Mar;91(1):12–20. doi: 10.1016/0008-8749(85)90027-9. [DOI] [PubMed] [Google Scholar]
- Hendricks R. L., Janowicz M., Tumpey T. M. Critical role of corneal Langerhans cells in the CD4- but not CD8-mediated immunopathology in herpes simplex virus-1-infected mouse corneas. J Immunol. 1992 Apr 15;148(8):2522–2529. [PubMed] [Google Scholar]
- Hendricks R. L., Sugar J. Lysis of herpes simplex virus-infected targets. II. Nature of the effector cells. Cell Immunol. 1984 Feb;83(2):262–270. doi: 10.1016/0008-8749(84)90305-8. [DOI] [PubMed] [Google Scholar]
- Hendricks R. L., Tao M. S., Glorioso J. C. Alterations in the antigenic structure of two major HSV-1 glycoproteins, gC and gB, influence immune regulation and susceptibility to murine herpes keratitis. J Immunol. 1989 Jan 1;142(1):263–269. [PubMed] [Google Scholar]
- Hendricks R. L., Tumpey T. M. Concurrent regeneration of T lymphocytes and susceptibility to HSV-1 corneal stromal disease. Curr Eye Res. 1991;10 (Suppl):47–53. doi: 10.3109/02713689109020357. [DOI] [PubMed] [Google Scholar]
- Hendricks R. L., Tumpey T. M. Contribution of virus and immune factors to herpes simplex virus type I-induced corneal pathology. Invest Ophthalmol Vis Sci. 1990 Oct;31(10):1929–1939. [PubMed] [Google Scholar]
- Hendricks R. L., Tumpey T. M., Finnegan A. IFN-gamma and IL-2 are protective in the skin but pathologic in the corneas of HSV-1-infected mice. J Immunol. 1992 Nov 1;149(9):3023–3028. [PubMed] [Google Scholar]
- Howie S., Norval M., Maingay J. Exposure to low-dose ultraviolet radiation suppresses delayed-type hypersensitivity to herpes simplex virus in mice. J Invest Dermatol. 1986 Feb;86(2):125–128. doi: 10.1111/1523-1747.ep12284128. [DOI] [PubMed] [Google Scholar]
- Jacobsen H., Mestan J., Mittnacht S., Dieffenbach C. W. Beta interferon subtype 1 induction by tumor necrosis factor. Mol Cell Biol. 1989 Jul;9(7):3037–3042. doi: 10.1128/mcb.9.7.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jinquan T., Larsen C. G., Gesser B., Matsushima K., Thestrup-Pedersen K. Human IL-10 is a chemoattractant for CD8+ T lymphocytes and an inhibitor of IL-8-induced CD4+ T lymphocyte migration. J Immunol. 1993 Nov 1;151(9):4545–4551. [PubMed] [Google Scholar]
- Lattime E. C., Stutman O. Antitumor immune surveillance by tumor necrosis factor producing cells. Immunol Res. 1991;10(2):104–113. doi: 10.1007/BF02918158. [DOI] [PubMed] [Google Scholar]
- Mestan J., Brockhaus M., Kirchner H., Jacobsen H. Antiviral activity of tumour necrosis factor. Synergism with interferons and induction of oligo-2',5'-adenylate synthetase. J Gen Virol. 1988 Dec;69(Pt 12):3113–3120. doi: 10.1099/0022-1317-69-12-3113. [DOI] [PubMed] [Google Scholar]
- Mestan J., Digel W., Mittnacht S., Hillen H., Blohm D., Möller A., Jacobsen H., Kirchner H. Antiviral effects of recombinant tumour necrosis factor in vitro. 1986 Oct 30-Nov 5Nature. 323(6091):816–819. doi: 10.1038/323816a0. [DOI] [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]
- Newell C. K., Martin S., Sendele D., Mercadal C. M., Rouse B. T. Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology. J Virol. 1989 Feb;63(2):769–775. doi: 10.1128/jvi.63.2.769-775.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Niemialtowski M. G., Rouse B. T. Predominance of Th1 cells in ocular tissues during herpetic stromal keratitis. J Immunol. 1992 Nov 1;149(9):3035–3039. [PubMed] [Google Scholar]
- Oppenheimer-Marks N., Davis L. S., Bogue D. T., Ramberg J., Lipsky P. E. Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes. J Immunol. 1991 Nov 1;147(9):2913–2921. [PubMed] [Google Scholar]
- Pereira R. A., Tscharke D. C., Simmons A. Upregulation of class I major histocompatibility complex gene expression in primary sensory neurons, satellite cells, and Schwann cells of mice in response to acute but not latent herpes simplex virus infection in vivo. J Exp Med. 1994 Sep 1;180(3):841–850. doi: 10.1084/jem.180.3.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Polla L., Margolis R., Goulston C., Parrish J. A., Granstein R. D. Enhancement of the elicitation phase of the murine contact hypersensitivity response by prior exposure to local ultraviolet radiation. J Invest Dermatol. 1986 Jan;86(1):13–17. doi: 10.1111/1523-1747.ep12283708. [DOI] [PubMed] [Google Scholar]
- Renkonen R., Mattila P., Majuri M. L., Paavonen T., Silvennoinen O. IL-4 decreases IFN-gamma-induced endothelial ICAM-1 expression by a transcriptional mechanism. Scand J Immunol. 1992 May;35(5):525–530. doi: 10.1111/j.1365-3083.1992.tb03251.x. [DOI] [PubMed] [Google Scholar]
- Rivas J. M., Ullrich S. E. Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes. An essential role for keratinocyte-derived IL-10. J Immunol. 1992 Dec 15;149(12):3865–3871. [PubMed] [Google Scholar]
- Ross J. A., Howie S. E., Norval M., Maingay J. Two phenotypically distinct T cells are involved in ultraviolet-irradiated urocanic acid-induced suppression of the efferent delayed-type hypersensitivity response to herpes simplex virus, type 1 in vivo. J Invest Dermatol. 1987 Sep;89(3):230–233. doi: 10.1111/1523-1747.ep12470977. [DOI] [PubMed] [Google Scholar]
- Rossol-Voth R., Rossol S., Schütt K. H., Corridori S., de Cian W., Falke D. In vivo protective effect of tumour necrosis factor alpha against experimental infection with herpes simplex virus type 1. J Gen Virol. 1991 Jan;72(Pt 1):143–147. doi: 10.1099/0022-1317-72-1-143. [DOI] [PubMed] [Google Scholar]
- Sciammas R., Johnson R. M., Sperling A. I., Brady W., Linsley P. S., Spear P. G., Fitch F. W., Bluestone J. A. Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell. J Immunol. 1994 Jun 1;152(11):5392–5397. [PubMed] [Google Scholar]
- Simmons A., Tscharke D. C. Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. J Exp Med. 1992 May 1;175(5):1337–1344. doi: 10.1084/jem.175.5.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simon J. C., Cruz P. D., Jr, Bergstresser P. R., Tigelaar R. E. Low dose ultraviolet B-irradiated Langerhans cells preferentially activate CD4+ cells of the T helper 2 subset. J Immunol. 1990 Oct 1;145(7):2087–2091. [PubMed] [Google Scholar]
- Thorbecke G. J., Shah R., Leu C. H., Kuruvilla A. P., Hardison A. M., Palladino M. A. Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7375–7379. doi: 10.1073/pnas.89.16.7375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tullo A. B., Shimeld C., Blyth W. A., Hill T. J., Easty D. L. Spread of virus and distribution of latent infection following ocular herpes simplex in the non-immune and immune mouse. J Gen Virol. 1982 Nov;63(Pt 1):95–101. doi: 10.1099/0022-1317-63-1-95. [DOI] [PubMed] [Google Scholar]
- Tumpey T. M., Elner V. M., Chen S. H., Oakes J. E., Lausch R. N. Interleukin-10 treatment can suppress stromal keratitis induced by herpes simplex virus type 1. J Immunol. 1994 Sep 1;153(5):2258–2265. [PubMed] [Google Scholar]
- Valyi-Nagy T., Deshmane S. L., Raengsakulrach B., Nicosia M., Gesser R. M., Wysocka M., Dillner A., Fraser N. W. Herpes simplex virus type 1 mutant strain in1814 establishes a unique, slowly progressing infection in SCID mice. J Virol. 1992 Dec;66(12):7336–7345. doi: 10.1128/jvi.66.12.7336-7345.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452. doi: 10.1146/annurev.iy.10.040192.002211. [DOI] [PubMed] [Google Scholar]
- Wilbanks G. A., Streilein J. W. Studies on the induction of anterior chamber-associated immune deviation (ACAID). 1. Evidence that an antigen-specific, ACAID-inducing, cell-associated signal exists in the peripheral blood. J Immunol. 1991 Apr 15;146(8):2610–2617. [PubMed] [Google Scholar]
- Williamson J. S., Bradley D., Streilein J. W. Immunoregulatory properties of bone marrow-derived cells in the iris and ciliary body. Immunology. 1989 May;67(1):96–102. [PMC free article] [PubMed] [Google Scholar]