Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus

Journal of Experimental Medicine

Volumn 187, Issue 11, 1998, Pages 1903-1920

  Binder, Daniel ^a   Van Den Broek, Maries F ^a   Kägi, David ^a   Bluethmann, Horst ^c   Fehr, Jörg ^b   Hengartner, Hans ^a   Zinkernagel, Rolf M ^a  

^a INSTITUTE OF EXPERIMENTAL IMMUNOLOGY   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^c F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Aplastic anemia; Cytokines; Cytotoxic lymphocytes; Immune tolerance; Lymphocytic choriomeningitis virus

Indexed keywords

CD8 ANTIGEN; CYTOKINE;

ANIMAL CELL; ANTIGEN EXPRESSION; APLASTIC ANEMIA; ARTICLE; BONE MARROW CELL; CYTOTOXIC T LYMPHOCYTE; IMMUNE RESPONSE; KNOCKOUT MOUSE; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; MOLECULAR INTERACTION; MOUSE; NONHUMAN; PANCYTOPENIA; PERSISTENT VIRUS INFECTION; PRIORITY JOURNAL; STEM CELL; T LYMPHOCYTE ACTIVATION;

ANEMIA, APLASTIC; ANIMALS; ANTIGENS, CD; BONE MARROW; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE; CYTOKINES; DISEASE MODELS, ANIMAL; ERYTHROCYTE COUNT; INTERFERON TYPE II; LYMPHOCYTIC CHORIOMENINGITIS; LYMPHOTOXIN-ALPHA; MEMBRANE GLYCOPROTEINS; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PANCYTOPENIA; PLATELET COUNT; PORE FORMING CYTOTOXIC PROTEINS; RECEPTORS, TUMOR NECROSIS FACTOR; RECEPTORS, TUMOR NECROSIS FACTOR, TYPE I; TUMOR NECROSIS FACTOR-ALPHA; VIRUS LATENCY; VIRUS REPLICATION;

EID: 0032101604     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.187.11.1903     Document Type: Article

References (62)

1. Kagan, W.A., J.A. Ascensao, R.N. Pahwa, J.A. Hansen, G. Goldstein, E.B. Valera, G.S. Incefy, M.A. Moore, and R.A. Good. 1976. Aplastic anemia: presence in human bone marrow of cells that suppress myelopoiesis. Proc. Natl. Acad. Sci. U.S.A. 73:2890-2894.
2. Young, N.S., and B.P. Alter. 1994. Aplastic anemia: acquired and inherited. W.B. Saunders, Philadelphia. 1-267.
3. Iishi, Y., M. Kosaka, T. Mizuguchi, K. Toyota, Y. Takaue, Y. Kawano, and S. Saito. 1991. Suppression of hematopoiesis by activated T-cells in infectious mononucleosis associated with pancytopenia. Int. J. Hematol. 54:65-73.
4. Shadduck, R.K., A. Winkelstein, Z. Zeigler, J. Lichter, M. Goldstein, M. Michaels, and B. Rabin. 1979. Aplastic anemia following infectious mononucleosis: possible immune etiology. Exp. Hematol. (NY). 7:264-271.
5. Apperley, J.F., C. Dowding, J. Hibbin, J. Buiter, E. Matutes, P.J. Sissons, M. Gordon, and J.M. Goldman. 1989. The effect of cytomegalovirus on hemopoiesis: in vitro evidence for selective infection of marrow stromal cells. Exp. Hematol. (NY). 17:38-45.
6. Reddehase, M.J., L. Dreher-Stumpp, P. Angele, M. Balthesen, and M. Susa. 1992. Hematopoietic stem cell deficiency resulting from cytomegalovirus infection of bone marrow stroma. Ann. Hematol. 64:A125-A127.
7. Molina J.-M., D.T. Scadden, M. Sakaguchi, B. Fuller, A. Woon, and J.E. Groopman. 1990. Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus. Blood. 76:2476-2482.
8. Brown, K.E., J. Tisdale, A.J. Barrett, C.E. Dunbar, and N.S. Young. 1997. Hepatitis-associated aplastic anemia. N. Engl. J. Med. 336:1059-1064.
9. Tzakis, A.G., M. Arditi, P.F. Whitington, K. Yanaga, C. Esquivel, W.A. Andrews, L. Makowka, J. Malatak, D.K. Freese, and P.G. Stock. 1988. Aplastic anemia complicating orthotopic liver transplantation for non-A, non-B hepatitis. N. Engl. J. Med. 319:393-396.
10. Albert, E., E.D. Thomas, B. Nispersos, and R. Storb. 1976. HLA antigens and haplotypes in 200 patients with aplastic anemia. Transplantation. 22:528-531.
11. Chapuis, B., V.E. Von Fliedner, M. Jeannet, H. Merica, P. Vuagnat, A. Gratwohl, C. Nissen, and B. Speck. 1986. Increased frequency of DR2 in patients with aplastic anaemia and increased DR sharing in their parents. Br. J. Haematol. 63:51-57.
12. Speck, B., A. Gratwohl, C. Nissen, U. Leibundgut, D. Ruggero, B. Osterwalder, H.P. Burri, P. Cornu, and M. Jeannet. 1981. Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation. Br. Med. J. 282:860-863.
13. Thomas, E.D., R. Storb, A. Fefer, S.J. Slichter, J.I. Bryant, C.D. Buckner, P.E. Neiman, R.A. Clift, D.D. Funk, and K.E. Lerner. 1972. Aplastic anaemia treated by marrow transplantation. Lancet. 1:284-289.
14. Young, N.S., and J. Maciejewski. 1997. The pathophysiology of acquired aplastic anemia. New. Engl. J. Med. 336:1365-1372.
15. Binder, D., J. Fehr, H. Hengartner, and R.M. Zinkernagel. 1997. Virus-induced transient bone marrow aplasia: major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus. J. Exp. Med. 185:517-530.
16. Müller, U., U. Steinhoff, L.F.L. Reis, S. Hemmi, J. Pavlovic, R.M. Zinkernagel, and M. Aguet. 1994. Functional role of type I and type II interferons in antiviral defense. Science. 264: 1918-1921.
17. Aichele, P., M.F. Bachmann, H. Hengartner, and R.M. Zinkernagel. 1996. Immunopathology or organ-specific autoimmunity as a consequence of virus infection. Immunol. Rev. 152:21-45.
18. Cole, G.A., N. Nathanson, and R.A. Prendergast. 1972. Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature. 238:335-337.
19. Zinkernagel, R.M., E. Haenseler, T. Leist, A. Cerny, H. Hengartner, and A. Althage. 1986. T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. J. Exp. Med. 164:1075-1092.
20. Leist, T.P., E. Rüedi, and R.M. Zinkernagel. 1988. Virus-triggered immune suppression in mice caused by virus-specific cytotoxic T cells. J. Exp. Med. 167:1749-1754.
21. Kägi, D., B. Odermatt, P.S. Ohashi, R.M. Zinkernagel, and H. Hengartner. 1996. Development of insulitis without diabetes in transgenic mice lacking perforin-dependent cytotoxicity. J. Exp. Med. 183:2143-2152.
22. Evans, C.F., M.S. Horwitz, M.V. Hobbs, and M.B. Oldstone. 1996. Viral infection of transgenic mice expressing a viral protein in oligodendrocytes leads to chronic central nervous system autoimmune disease. J. Exp. Med. 184:2371-2384.
23. Hotchin, J. 1962. The biology of lymphocytic choriomeningitis infection: virus induced immune disease. Cold Spring Harhor Symp. Quant. Biol. 27:479-499.
24. Pfau, C.J., J.K. Valenti, D.C. Pevear, and K.D. Hunt. 1982. Lymphocytic choriomeningitis virus killer T cells are lethal only in weakly disseminated murine infections. J. Exp. Med. 156:79-89.
25. Muller, D., B.H. Koller, J.L. Whitton, K.E. LaPan, K.K. Brigman, and J.A. Frelinger. 1992. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Science. 255:1576-1578.
26. Harrison, D.E., C.M. Astle, and C. Lerner. 1988. Number and continuous proliferative pattern of transplanted primitive immunohematopoietic stem cells. Proc. Natl. Acad. Sci. U.S.A. 85:822-826.
27. Kägi, D., B. Ledermann, K. Bürki, P. Seiler, B. Odermatt, K.J. Olsen, E.R. Podack, R.M. Zinkernagel, and H. Hensrartner. 1994. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 369:31-37.
28. Rothe, J., W. Lesslauer, H. Lotscher, Y. Lang, P. Koebel, F. Kontgen, A. Althage, R. Zinkernagel, M. Steinmetz, and H. Bluethmann. 1993. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature. 364: 798-802.
29. Lehmann-Grube, F. 1971. Lymphocytic choriomeningitis virus. Monogr. Virol. 10:1-173.
30. Battegay, M., S. Cooper, A. Althage, J. Baenziger, H. Hengartner, and R.M. Zinkernagel. 1991. Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24 or 96 well plates. J. Virol. Methods. 33:191-198.
31. Cobbold, S.P., A. Jayasuriya, A. Nash, T.D. Prospero, and H. Waldmann. 1984. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 312:548-551.
32. Leist, T.P., M. Eppler, and R.M. Zinkernagel. 1989. Enhanced virus replication and inhibition of lymphocytic choriomeningitis disease in anti-gamma interferon-treated mice. J. Virol. 63:2813-2819.
33. Zinkernagel, R.M., T.P. Leist, H. Hengartner, and A. Althage. 1985. Susceptibility to lymphocytic choriomeningitis virus isolates correlates directly with early and cytotoxic T cell activity, as well as with footpad swelling reaction, and all three are regulated by H-2D. J. Exp. Med. 162:2125-2141.
34. Pruslin, F.H. 1991. Caveats and suggestions for the ELISA. J. Immunol. Methods. 137:27-35.
35. Kägi, D., B. Ledermann, K. Bürki, R.M. Zinkernagel, and H. Hengartner. 1995. Lymphocyte-mediated cytotoxicity in vitro and in vivo: mechanisms and significance. Immunol. Rev. 146:95-115.
36. Murphy, M., R. Loudon, M. Kobayashi, and G. Trinchieri. 1986. Gamma-interferon and lymphotoxin released by activated T cells synergize to inhibit granulocyte/monocyte colony formation. J. Exp. Med. 164:263-279.
37. Zoumbos, N.C., W.O. Ferris, S.M. Hsu, S. Goodman, P. Griffith, S.O. Sharrow, R.K. Humphries, A.W. Nienhuis, and N. Young. 1984. Analysis of lymphocyte subsets in patients with aplastic anaemia. Br. J. Haematol. 58:95-105.
38. Nakao, S., M. Yamaguchi, S. Shiobara, T. Yokoi, T. Miyawaki, T. Taniguchi, and T. Matsuda. 1992. Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia. Blood. 79:2532-2535.
39. Zoumbos, N.C., P. Gascon, J.Y. Djeu, and N.S. Young. 1985. Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proc. Natl. Acad. Sci. U.S.A. 82:188-192.
40. Viale, M., A. Merli, and A. Bacigalupo. 1991. Analysis at the clonal level of T-cell phenotype and functions in severe aplastic anemia patients. Blood. 78:1268-1274.
41. Ahmed, R., A. Salmi, L.D. Butler, J.M. Chiller, and M.B. Oldstone. 1984. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J. Exp. Med. 160:521-540.
42. Borrow, P., C.F. Evans, and M.B. Oldstone. 1995. Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression. J. Virol. 69:1059-1070.
43. Moebius, U., F. Herrmann, T. Hercend, and S.C. Meuer. 1991. Clonal analysis of CD4+/CD8+ T cells in a patient with aplastic anemia. J. Clin. Invest. 87:1567-1574.
44. Pfeffer, K., T. Matsuyama, T.M. Kündig, A. Wakeham, K. Kishihara, A. Shahinian, K. Wiegmann, P.S. Ohashi, M. Kronke, and T.W. Mak. 1993. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 73: 457-467.
45. Tartaglia, L.A., and D.V. Goeddel. 1992. Two TNF receptors. Immunol. Today. 13:151-153.
46. Johnson, C.S., M.J. Chang, and F. Furmanski. 1988. In vivo hematopoietic effects of tumor necrosis factor-alpha in normal and erythroleukemic mice: characterization and therapeutic applications. Blood. 72:1875-1883.
47. Ohashi, P.S., S. Oehen, P. Aichele, H. Pircher, B. Odermatt, P. Herrera, Y. Higuchi, K. Buerki, H. Hengartner, and R.M. Zinkernagel. 1993. Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-alpha. J. Immunol. 150:5185-5194.
48. Guidotti, L.G., P. Borrow, M.V. Hobbs, B. Matzke, I. Gresser, M.B. Oldstone, and F.V. Chisari. 1996. Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver. Proc. Natl. Acad. Sci. U.S.A. 93:4589-4594.
49. Sieff, C.A., C.M. Niemeyer, S.J. Mentzer, and D.V. Faller. 1988. Interleukin-1, tumor necrosis factor, and the production of colony-stimulating factors by cultured mesenchymal cells. Blood. 72:1316-1323.
50. Broxmeyer, H.E., L. Lu, E. Platzer, C. Feit, L. Juliano, and B.Y. Rubin. 1983. Comparative analysis of the influences of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. J. Immunol. 131:1300-1305.
51. Seileri, C., J.P. Maciejewski, T. Sato, and N.S. Young. 1996. Interferon-gamma constitutively expressed in the stromal microenvironment of human marrow cultures mediates potent hematopoietic inhibition. Blood. 87:4149-4157.
52. Collart, M.A., D. Belin, J.D. Vassalli, S. de Kossodo, and P. Vassalli. 1986. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokmase genes, which are controlled by short-lived repressors. J. Exp. Med. 164:2113-2118.
53. Collins, T., A.J. Korman, C.T. Wake, J.M. Boss, D.J. Kappes, W. Fiers, K.A. Ault, M.A. Gimbrone, Jr., J.L. Strominger, and J.S. Pober. 1984. Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc. Natl. Acad. Sci. U.S.A. 81: 4917-4921.
54. Huang, S., W. Hendriks, A. Althage, S. Hemmi, H. Bluethinann, R. Kamijo, J. Vilcek, R.M. Zinkernagel, and M. Aguet. 1993. Immune response in mice that lack the interferon-gamma receptor. Science. 259:1742-1745.
55. Speiser, D.E., E. Sebzda, T. Ohteki, M.F. Bachmann, K. Pfeffer, T.W. Mak, and P.S. Ohashi. 1996. Tumor necrosis factor receptor p55 mediates deletion of peripheral cytotoxic T lymphocytes in vivo. Eur. J. Immunol. 26:3055-3060.
56. Guidotti, L.G., T. Ishikawa, M.V. Hobbs, B. Matzke, R. Schreiber, and F.V. Chisari. 1996. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity. 4:25-36.
57. Knospe, W.H., D. Steinberg, and B. Speck. 1983. Experimental immunologically mediated aplastic anemia (AA) in H-2k identical, Mls (M) locus different mice. Exp. Hematol. (NY). 11:542-552.
58. Sprent, J., C.D. Surh, D. Agus, M. Hurd, S. Sutton, and W.R. Heath. 1994. Profound atrophy of the bone marrow reflecting major histocompatibility complex class II-restricted destruction of stem cells by CD4+ cells. J. Exp. Med. 180:307-317.
59. Hotchin, J.E. 1971. Persistent and slow virus infections. Monogr. Virol. 3:1-211.
60. Peralta, L.A.M., C.E. Coto, and M.C. Weissenbacher. 1993. The Tacaribe complex: the close relationship between a pathogenic (junin) and a nonpathogenic (tacaribe) arenavirus. In The Arenavindae. M.S. Salvato, editor. Pelnum Press, New York. 281-298.
61. Holmberg, L.A., K. Seidel, W. Leisenring, and B. Torok-Storb. 1994. Aplastic anemia: analysis of stromal cell function in long-term marrow cultures. Blood. 84:3683-3690.
62. Cashman, J.D., A.C. Eaves, E.W. Raines, R. Ross, and C.J. Eaves. 1990. Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. I. Stimulatory role of a variety of mesenchymal cell activators and inhibitory role of TGF-beta. Blood. 75: 96-101.