Advertisement

Therapeutic Reconstitution of Human Viral Immunity by Adoptive Transfer of Cytotoxic T Lymphocyte Clones

  • S. R. Riddell
  • P. D. Greenberg
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 189)

Abstract

The fundamental role of a competent host T lymphocyte response for promoting the resolution of acute viral infections is supported by the severe and progressive infections observed in individuals with primary or acquired deficiencies of T cell function (Rosen et al. 1984a, b; Redfield et al. 1987; Englund et al. 1988; Ljungman et al. 1989). The critical immune response is comprised of CD8+ cytotoxic T cells (CTL) and CD4+ helper T cells (Th), which recognize degraded fragments of proteins derived from pathogens and presented in association with class I and class II major histocompatibility complex (MHC) molecules, respectively (Braciale et al. 1987; Yewdell and Bennink 1990). CD8+ CTL function to eradicate viral infection by the direct lysis of infected cells and by the secretion of cytokines such as γ-interferon. The predominant function of CD4+ Th in the host response to infection is the production of cytokines, which in addition to direct antiviral effects facilitate the antiviral activities of macrophages, B cells, and other T cells including CD8+ CTL.

Keywords

Major Histocompatibility Complex Adoptive Transfer Adoptive Immunotherapy Bone Marrow Donor Human Viral Immunity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Borysiewicz LK, Morris S, Page J, Sissons JGP (1983) Human cytomegalovirus-specific cytotoxic T lymphocytes: requirements for in vitro generation and specificity. Eur J Immunol 13:804–809PubMedCrossRefGoogle Scholar
  2. Borysiewicz LK, Graham S, Hickling JK, Sissons JGP (1988a) Precursor frequency and stage specificity of human cytomegalovirus-specific cytotoxic T cells. Eur J Immunol 18: 269–275PubMedCrossRefGoogle Scholar
  3. Borysiewicz LK, Hickling JK, Graham S, Sinclair J, Cranage MP, Smith GL, Sissons JGP (1988b) Human cytomegalovirus-specific cytotoxic T cells: relative frequency of stage- specific CTL recognizing the 72 KD immediate early protein and glycoprotein B expressed by recombinant vaccina viruses. J Exp Med 168: 919–932PubMedCrossRefGoogle Scholar
  4. Braciale TJ, Morrison LA, Sweetser MJ, Sambrook J, Gething MJ, Braciale VL (1987) Antigen presentation pathways to class I and class II MHC restricted T lymphocytes. Immunol Rev 98:94–114CrossRefGoogle Scholar
  5. Byrne JA, Oldstone MBA (1984) Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J Virol 51:682–686PubMedGoogle Scholar
  6. Cannon MD, Stott EJ, Taylor G, Askonsas BA (1987) Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology 62:133–139PubMedGoogle Scholar
  7. Chandler SH, McDougall JK (1986) Comparison of restriction site polymorphisms among clinical isolates and laboratory strains of human cytomegalovirus. J Gen Virol 67: 2179–21 92Google Scholar
  8. Cheever MA, Greenberg PD, Fefer A, Gillis S (1982) Augmentation of the antitumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. J Exp Med 155:968–980PubMedCrossRefGoogle Scholar
  9. Cheever MA, Thompson DB, Klarnet JP, Greenberg PD (1986) Antigen-driven long-term cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy and persist long term as functional memory T cells. J Exp Med 163:1100–1112PubMedCrossRefGoogle Scholar
  10. Chou SW (1986) Acquisition of donor strains of CMV by renal transplant patients. N Engl J Med 314:1418–1423PubMedCrossRefGoogle Scholar
  11. Chou SW, Dennison DM (1991) Analysis of interstrain variation in cytomegalovirus glycoprotein B sequences encoding neutralization-related epitopes. J Infect Dis 163:1229–1234PubMedCrossRefGoogle Scholar
  12. Emmanuel D, Cunningham I, Joles-Elysec K, Brochstein JA, Kernan NA, Laver J, Stover D, White DA, Fels A, Polsky G, Castro-Malaspina H, Peppard JR, Bartus P, Hammerling U, O’Reilly RJ (1988) Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high dose intravenous immune globulin. Ann Intern Med 109:777–782Google Scholar
  13. Englund JA, Sullivan CJ, Jordan MC (1988) Respiratory syncytical virus infection in immunocompromised adults. Ann Intern Med 109:203–208PubMedGoogle Scholar
  14. Erice A, Chou SW, Biron K, Stanat SC, Balfour HH, Jordan MC (1989) Progressive disease due to ganciclovir—resistant cytomegalovirus in immunocompromised patients. N Engl J Med 320:289–293PubMedCrossRefGoogle Scholar
  15. Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P (1990) Interleukin 2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397–403PubMedCrossRefGoogle Scholar
  16. Fisher B, Packard BS, Reed EF, Caraquillo JA, Carter CS, Topalian SL, Yang SC, Yolles P, Larson JM, Rosenberg SA (1989) Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J Clin Oncol 7: 250–261PubMedGoogle Scholar
  17. Gardner MB, Officer JE, Parker J, Estes JD, Rongey RW (1974) Induction of disseminated virulent cytomegalovirus infection by immunosuppression of naturally chronically infected wild mice. Infect Immun 10:966–969PubMedGoogle Scholar
  18. Golumbek PT, Lazenby AJ, Levitsky HI, Jaffee LM, Karasuyama H, Baker M, Pardoll DM (1991) Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 254:713–716PubMedCrossRefGoogle Scholar
  19. Gooding LR (1992) Virus proteins that counteract host immune defenses. Cell 71:5–7PubMedCrossRefGoogle Scholar
  20. Goodrich JM, Mori M, Gleaves CA, DuMond C, Cays M, Ebeling DF, Bühles WC, deArmond B, Meyers JD (1991) Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med 325:1601–1607PubMedCrossRefGoogle Scholar
  21. Greenberg PD (1986) Therapy of murine leukemia with cyclophosphamide and immune Lyt 2 + cells: cytolytic T cells can mediate eradication of disseminated leukemia. J Immunol 136: 1917–1922PubMedGoogle Scholar
  22. Greenberg PD (1991) Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. Adv Immunol 49:281–335PubMedCrossRefGoogle Scholar
  23. Greenberg PD, Kern DE, Cheever MA (1985) Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+2- T cells: tumor eradication does not require participation of cytotoxic T cells. J Exp Med 161:1122–1135PubMedCrossRefGoogle Scholar
  24. Greenberg PD, Reusser P, Goodrich J M, Riddell SR (1991) Development of a treatment regimen for human cytomegalovirus (CMV) infection in bone marrow transplantation recipients by adoptive transfer of donor-derived CMV-specific T cell clones expanded in vitro. Ann NY Acad Sci 636:184–195CrossRefGoogle Scholar
  25. Guillaume JC, Sasaz P, Wechsler J, Lescs MD, Rouzeau JC (1991) Vaccinia from recombinant virus expressing HIV genes. Lancet 337:1034–1035PubMedCrossRefGoogle Scholar
  26. Griffiths PD, Grundy JC (1987) Molecular biology and immunology of cytomegalovirus. Biochem J 241:313–324PubMedGoogle Scholar
  27. Huang E-S, Alford CA, Reynolds DW, Stagno S, Pass RF (1980) Molecular epidemiology of cytomegalovirus infections in women and their infants. N Engl J Med 303:958–962PubMedCrossRefGoogle Scholar
  28. Jacobson MA, Mills J (1988) Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 108: 585–594PubMedGoogle Scholar
  29. Jahn G, Scholl B-C, Traupe B, Fleckenstein B (1987) The two major structural phosphoproteins (pp65 and pp150) of human cytomegalovirus and their antigenic properties. J Gen Virol 68:1327–1337PubMedCrossRefGoogle Scholar
  30. Jordan MC, Shanley JD, Stevens JG (1977) Immunosuppression reactivates and disseminates latent murine cytomegalovirus. J Gen Virol 37:419–423PubMedCrossRefGoogle Scholar
  31. Koszinowski UH, Keil GM, Schwarz H, Schickedanz J, Reddehase MJ (1987) A nonstructural polypeptide encoded by immediate early transcription unit I of murine cytomegalovirus is recognized by cytolytic T lymphocytes. J Exp Med 166:289–294PubMedCrossRefGoogle Scholar
  32. Landini M-P, Michelson S (1988) Human cytomegalovirus proteins. Prog Med Virol 35: 152–185PubMedGoogle Scholar
  33. Larsen HS, Feng MF, Horohov DW, Moore RN, Rouse BT (1984) Role of T lymphocyte subsets in recovery from herpes simplex virus infection. J Virol 51:682–686Google Scholar
  34. Laubscher A, Bluestein HG, Spector SA, Zvaifler NJ (1988) Generation of human cytome- galovirus-specific cytotoxic T lymphocytes in a short-term culture. J Immunol Methods 110:69–77PubMedCrossRefGoogle Scholar
  35. Lenardo M (1991) Interleukin-2 programs mouse T lymphocytes for apoptosis. Nature 353:858–861PubMedCrossRefGoogle Scholar
  36. Ljungman P, Gleaves CA, Meyers JD (1989) Respiratory virus infection in immunocompromised patients. Bone Marrow Transplant 4:35–40PubMedGoogle Scholar
  37. Lukacher AE, Braciale VL, Braciale TF (1984) In vivo effector function of influenza virus-specific T lymphocyte clones is highly specific. J Exp Med 160:814–823PubMedCrossRefGoogle Scholar
  38. Lum LG (1987) The kinetics of immune reconstitution after human bone marrow transplantation. Blood 69:369–380PubMedGoogle Scholar
  39. Martin PJ, Shulman HM, Schubach WH, Hansen JA, Fefer A, Miller G, Thomas ED (1984) Fatal Epstein-Barr virus-associated proliferation of donor B cells after treatment of graft versus host disease with a murine anti T cell antibody. Ann Intern Med 101:310–315PubMedGoogle Scholar
  40. Meyers JD, Flournoy N, Thomas ED (1980) Cytomegalovirus infection and specific cellmediated immunity after marrow transplant. J Infect Dis 142: 816–824PubMedCrossRefGoogle Scholar
  41. Meyers JD, Flournoy N, Thomas ED (1986) Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis 153:478–488PubMedCrossRefGoogle Scholar
  42. Meyers JD, Bowden RA, Counts GW (1987) Infections after bone marrow transplantation. In: Lode H, Huhn D, Melzahn M (eds) Infections in transplant patients. Thieme, Stuttgart, pp17–32Google Scholar
  43. Meyers JD, Ljungmann P, Fisher LD (1990) Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia. J Infect Dis 162:373–380PubMedCrossRefGoogle Scholar
  44. Moore MW, Carbone FR, Bevan MJ (1988) Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell 54: 777–785PubMedCrossRefGoogle Scholar
  45. Mutter W, Reddehase MJ, Busch FW, Behring HJ, Koszinowski UH (1988) Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovorus disease in the immunocompromised host. J Exp Med 167:1645–1658PubMedCrossRefGoogle Scholar
  46. Posavad CM, Rosenthal KL (1992) Herpes simplex virus-infected human fibroblasts are resistant to and inhibit cytotoxic T lymphocyte activity. J Virol 66:6264–6272PubMedGoogle Scholar
  47. Purtilo DT (1980) Epstein Barr virus induced oncogenesis in immunodeficient individuals. Lancet 1:300–303PubMedCrossRefGoogle Scholar
  48. Quinnan GV, Kirmani N, Esber E, Sarai R, Manischewitz JF, Rogers JL, Rook AH, Santos GW, Burns WH (1981) HLA-restricted cytotoxic T lymphocytes and non thymic cytotoxic lymphocyte responses to cytomegalovirus infection in bone marrow transplant recipients. J Immunol 126:2031–2041Google Scholar
  49. Quinnan GV, Kirmani N, Rook AH, Manischewitz JF, Jackson L, Moreschi G, Santos GW, Sarai R, Burns WH (1982) HLA-restricted cytotoxic T lymphocytes and non thymic cytotoxic lymphocyte responses to cytomegalovirus infection. N Engl J Med 307: 6–13CrossRefGoogle Scholar
  50. Rasmussen L (1990) Immune responses to human cytomegalovirus infection. In: McDougall JK (ed) Cytomegaloviruses. Springer, Berlin Heidelberg New York, pp 221–254 (Current topics in microbiology and immunology, vol 154)Google Scholar
  51. Reddehase MJ, Koszinowski UH (1984) Significance of herpse virus immediate early gene expression in cellular immunity to cytomegalovirus infection. Nature 312:369–371PubMedCrossRefGoogle Scholar
  52. Reddehase MJ, Weiland F, Munch K, Jonjic S, Luske A, Koszinowski UH (1985) Interstitial murine CMV pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. J Virol 55:264–273PubMedGoogle Scholar
  53. Reddehase MJ, Mutter W, Munch K, Buhring H-J, Koszinowski UH (1987a) CD8-positive T lymphocytes specific for murine cytomegalovirus immediate early antigens mediate protective immunity. J Virol 61:3102–3108PubMedGoogle Scholar
  54. Reddehase MJ, Mutter W, Koszinowski UH (1987b) In vivo application of recombinant interleukin-2 in the immunotherapy of established cytomegalovirus infection. J Exp Med 165:650–656PubMedCrossRefGoogle Scholar
  55. Reddehase MJ, Rothbard JB, Koszinowski UH (1989) A pentapeptide as minimal antigenic determinant for MHC class I restricted lymphocytes. Nature 337:651–653PubMedCrossRefGoogle Scholar
  56. Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DJ (1987) Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 316: 673–676PubMedCrossRefGoogle Scholar
  57. Reed EC, Bowden RA, Dandliker PS, Lilleby KE, Meyers JD (1988) Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous immunoglobulin in patients with bone marrow transplants. Ann Intern Med 109:783–788PubMedGoogle Scholar
  58. Reusser P, Riddell SR, Meyers JD, Greenberg PD (1991) Cytotoxic T lymphocyte response to cytomegalovirus following allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 78:1373–1380PubMedGoogle Scholar
  59. Riddell SR, Greenberg PD (1990) The use of anti CD3 and anti CD28 monoclonal antibodies to clone and expand antigen-specific T cells. J Immunol Methods 128:189–197PubMedCrossRefGoogle Scholar
  60. Riddell SR, Reusser P, Greenberg PD (1991 a) Cytotoxic T cells specific for cytomegalovirus: a potential therapy for immunocompromised hosts. Rev Infect Dis 13: 966–973CrossRefGoogle Scholar
  61. Riddell SR, Rabin M, Geballe AP, Britt WJ, Greenberg PD (1991b) Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression. J Immunol 146:2795–2804PubMedGoogle Scholar
  62. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD (1992a) Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 257:238–241PubMedCrossRefGoogle Scholar
  63. Riddell SR, Greenberg PD, Overell RW, Loughran TP, Gilbert MJ, Lupton SD, Agosti J, Scheeler S, Coombs RW, Corey L (1992b) Phase I study of cellular adoptive immunotherapy using genetically modified CD8+ HIV-specific T cells for HIV seropositive patients undergoing allogeneic bone marrow transplant. Human Gene Ther 3: 319–338CrossRefGoogle Scholar
  64. Rosen FS, Cooper MD, Wedgewood RJP (1984a) The primary immunodeficiencies (part 1). N Engl J Med 311:235–242PubMedCrossRefGoogle Scholar
  65. Rosen FS, Cooper MD, Wedgewood RJP (1984b) The primary immunodeficiencies (part 2). N Engl J Med 311:300–310PubMedCrossRefGoogle Scholar
  66. Rosenberg SA, Lotze MT, Muul LM et al. (1985) Observations on the systemic dministration of autologous lymphokine-activated killer cells and recombinant IL2 for patients with meta- stasic cancer. N Engl J Med 313:1485–1492PubMedCrossRefGoogle Scholar
  67. Rosenberg SA, Lotze MT, Muul LM et al. (1986) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 316:1310–1321Google Scholar
  68. Rosenberg SA, Packard BS, Aebersold PM, Solomon D et al. (1988) Use of tumor-infiltrating lymphocytes and I L-2 in the immunotherapy of patients with metastatic melanoma: a preliminary report. N Engl J Med 319:1676–1680PubMedCrossRefGoogle Scholar
  69. Rosenberg SA, Aebersold P, Cornetta K, Kasid A, Morgan RA, Moen R, Karson EM, Lotze MT, Yang JC, Topalian SL, Merino MJ, Culver K, Miller AD, Blaese MR, Anderson WF (1990) Gene transfer into humans: immunotherapy of patients with advanced melanoma using tumor infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 323: 570–578PubMedCrossRefGoogle Scholar
  70. Sarai R, Burns WH, Laskin OL, Santos GW, Lietman PS (1981) Acyclovir prophylaxis of herpes simplex virus infections: a randomized, double blind controlled trial in bone marrow transplant recipients. N Engl J Med 305: 63–67CrossRefGoogle Scholar
  71. Schmidt GM, Horak DA, Niland JC, Dancan SR, Forman SJ, Zaia JA (1991) A randomized controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants. N Engl J Med 324:1005–1011PubMedCrossRefGoogle Scholar
  72. Schrier RD, Oldstone MBA (1986). Recent clinical isolation of CMV suppress human CMV- specific human leukocyte antigen-restricted cytotoxic T lymphocyte activity. J Virol 59: 127–132PubMedGoogle Scholar
  73. Shanley JD, Jordan MC, Cook ML, Stevens JG (1979) Pathogenesis of reactivated latentGoogle Scholar
  74. murine cytomegalovirus infection. Am J Pathol 95:67–77Google Scholar
  75. Stinski MF, Thornsen DR, Stenberg RM, Goldstein LC (1983) Organization and expression of the immediate early genes on human cytomegalovirus. J Virol 46:1–14PubMedGoogle Scholar
  76. Van Bleek GM, Nathenson SG (1990) Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature 348:213–216PubMedCrossRefGoogle Scholar
  77. Van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254:1643–1647PubMedCrossRefGoogle Scholar
  78. Walthen M, Stinski M (1982) Temporal patterns of human cytomegalovirus transcription: mapping the viral RNAs synthesized at immediate early, early, and late times after infection. J Virol 42: 462–467Google Scholar
  79. Witherspoon RP, Lum LG, Storb R (1984) Immunologic reconstitution after human marrow grafting. Semin Hematol 21:2–10PubMedGoogle Scholar
  80. Wold WSM, Gooding LR (1991) Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology 184:1–8PubMedCrossRefGoogle Scholar
  81. Yewdell JW, Bennick JR (1990) The binary logic of antigen processing and presentation to T cells. Cell 62:203–206PubMedCrossRefGoogle Scholar
  82. Yewdell JW, Bennick JR, Hosaka Y (1988) Cells process exogenous proteins for recognition by cytotoxic T lymphocytes. Science 239:637–640PubMedCrossRefGoogle Scholar
  83. Zutter MM, Martin P, Sale GE, Shulman HM, Fisher L, Thomas ED, Durnam D (1988) Epstein Barr virus lymphoproliferation after bone marrow transplantation. Blood 72:520–529PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • S. R. Riddell
    • 1
  • P. D. Greenberg
    • 1
  1. 1.Fred Hutchinson Cancer Research Center and the Departments of Medicine and ImmunologyUniversity of WashingtonSeattleUSA

Personalised recommendations