Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Apr 1;99(7):1472–1477. doi: 10.1172/JCI119308

Cytotoxic T cells and viral hepatitis.

F V Chisari 1
PMCID: PMC507965  PMID: 9119989

Full Text

The Full Text of this article is available as a PDF (103.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alcamí A., Smith G. L. Cytokine receptors encoded by poxviruses: a lesson in cytokine biology. Immunol Today. 1995 Oct;16(10):474–478. doi: 10.1016/0167-5699(95)80030-1. [DOI] [PubMed] [Google Scholar]
  2. Ando K., Guidotti L. G., Wirth S., Ishikawa T., Missale G., Moriyama T., Schreiber R. D., Schlicht H. J., Huang S. N., Chisari F. V. Class I-restricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo. J Immunol. 1994 Apr 1;152(7):3245–3253. [PubMed] [Google Scholar]
  3. Ando K., Moriyama T., Guidotti L. G., Wirth S., Schreiber R. D., Schlicht H. J., Huang S. N., Chisari F. V. Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis. J Exp Med. 1993 Nov 1;178(5):1541–1554. doi: 10.1084/jem.178.5.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ballardini G., Groff P., Pontisso P., Giostra F., Francesconi R., Lenzi M., Zauli D., Alberti A., Bianchi F. B. Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C. J Clin Invest. 1995 May;95(5):2067–2075. doi: 10.1172/JCI117893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barnaba V., Franco A., Paroli M., Benvenuto R., De Petrillo G., Burgio V. L., Santilio I., Balsano C., Bonavita M. S., Cappelli G. Selective expansion of cytotoxic T lymphocytes with a CD4+CD56+ surface phenotype and a T helper type 1 profile of cytokine secretion in the liver of patients chronically infected with Hepatitis B virus. J Immunol. 1994 Mar 15;152(6):3074–3087. [PubMed] [Google Scholar]
  6. Battegay M., Fikes J., Di Bisceglie A. M., Wentworth P. A., Sette A., Celis E., Ching W. M., Grakoui A., Rice C. M., Kurokohchi K. Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. J Virol. 1995 Apr;69(4):2462–2470. doi: 10.1128/jvi.69.4.2462-2470.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bertoletti A., Costanzo A., Chisari F. V., Levrero M., Artini M., Sette A., Penna A., Giuberti T., Fiaccadori F., Ferrari C. Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope. J Exp Med. 1994 Sep 1;180(3):933–943. doi: 10.1084/jem.180.3.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bertoletti A., Ferrari C., Fiaccadori F., Penna A., Margolskee R., Schlicht H. J., Fowler P., Guilhot S., Chisari F. V. HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10445–10449. doi: 10.1073/pnas.88.23.10445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bertoletti A., Sette A., Chisari F. V., Penna A., Levrero M., De Carli M., Fiaccadori F., Ferrari C. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature. 1994 Jun 2;369(6479):407–410. doi: 10.1038/369407a0. [DOI] [PubMed] [Google Scholar]
  10. Brunetto M. R., Giarin M. M., Oliveri F., Chiaberge E., Baldi M., Alfarano A., Serra A., Saracco G., Verme G., Will H. Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4186–4190. doi: 10.1073/pnas.88.10.4186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cerny A., McHutchison J. G., Pasquinelli C., Brown M. E., Brothers M. A., Grabscheid B., Fowler P., Houghton M., Chisari F. V. Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. J Clin Invest. 1995 Feb;95(2):521–530. doi: 10.1172/JCI117694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chazouillères O., Mamish D., Kim M., Carey K., Ferrell L., Roberts J. P., Ascher N. L., Wright T. L. "Occult" hepatitis B virus as source of infection in liver transplant recipients. Lancet. 1994 Jan 15;343(8890):142–146. doi: 10.1016/s0140-6736(94)90934-2. [DOI] [PubMed] [Google Scholar]
  13. Chisari F. V., Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol. 1995;13:29–60. doi: 10.1146/annurev.iy.13.040195.000333. [DOI] [PubMed] [Google Scholar]
  14. Davis G. L., Hoofnagle J. H., Waggoner J. G. Acute type A hepatitis during chronic hepatitis B virus infection: association of depressed hepatitis B virus replication with appearance of endogenous alpha interferon. J Med Virol. 1984;14(2):141–147. doi: 10.1002/jmv.1890140208. [DOI] [PubMed] [Google Scholar]
  15. Erickson A. L., Houghton M., Choo Q. L., Weiner A. J., Ralston R., Muchmore E., Walker C. M. Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C. J Immunol. 1993 Oct 15;151(8):4189–4199. [PubMed] [Google Scholar]
  16. Farci P., Alter H. J., Govindarajan S., Wong D. C., Engle R., Lesniewski R. R., Mushahwar I. K., Desai S. M., Miller R. H., Ogata N. Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992 Oct 2;258(5079):135–140. doi: 10.1126/science.1279801. [DOI] [PubMed] [Google Scholar]
  17. Farci P., Alter H. J., Wong D. C., Miller R. H., Govindarajan S., Engle R., Shapiro M., Purcell R. H. Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7792–7796. doi: 10.1073/pnas.91.16.7792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fischer M., Runkel L., Schaller H. HBx protein of hepatitis B virus interacts with the C-terminal portion of a novel human proteasome alpha-subunit. Virus Genes. 1995;10(1):99–102. doi: 10.1007/BF01724303. [DOI] [PubMed] [Google Scholar]
  19. Franco A., Ferrari C., Sette A., Chisari F. V. Viral mutations, TCR antagonism and escape from the immune response. Curr Opin Immunol. 1995 Aug;7(4):524–531. doi: 10.1016/0952-7915(95)80098-0. [DOI] [PubMed] [Google Scholar]
  20. Galle P. R., Hofmann W. J., Walczak H., Schaller H., Otto G., Stremmel W., Krammer P. H., Runkel L. Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med. 1995 Nov 1;182(5):1223–1230. doi: 10.1084/jem.182.5.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Guidotti L. G., Borrow P., Hobbs M. V., Matzke B., Gresser I., Oldstone M. B., Chisari F. V. 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. 1996 May 14;93(10):4589–4594. doi: 10.1073/pnas.93.10.4589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Guidotti L. G., Ishikawa T., Hobbs M. V., Matzke B., Schreiber R., Chisari F. V. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity. 1996 Jan;4(1):25–36. doi: 10.1016/s1074-7613(00)80295-2. [DOI] [PubMed] [Google Scholar]
  23. Guidotti L. G., Matzke B., Pasquinelli C., Shoenberger J. M., Rogler C. E., Chisari F. V. The hepatitis B virus (HBV) precore protein inhibits HBV replication in transgenic mice. J Virol. 1996 Oct;70(10):7056–7061. doi: 10.1128/jvi.70.10.7056-7061.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hasegawa K., Huang J., Rogers S. A., Blum H. E., Liang T. J. Enhanced replication of a hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. J Virol. 1994 Mar;68(3):1651–1659. doi: 10.1128/jvi.68.3.1651-1659.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hiramatsu N., Hayashi N., Katayama K., Mochizuki K., Kawanishi Y., Kasahara A., Fusamoto H., Kamada T. Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C. Hepatology. 1994 Jun;19(6):1354–1359. [PubMed] [Google Scholar]
  26. Inoue M., Kakumu S., Yoshioka K., Tsutsumi Y., Wakita T., Arao M. Hepatitis B core antigen-specific IFN-gamma production of peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection. J Immunol. 1989 Jun 1;142(11):4006–4011. [PubMed] [Google Scholar]
  27. Jung M. C., Diepolder H. M., Spengler U., Wierenga E. A., Zachoval R., Hoffmann R. M., Eichenlaub D., Frösner G., Will H., Pape G. R. Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection. J Virol. 1995 Jun;69(6):3358–3368. doi: 10.1128/jvi.69.6.3358-3368.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kakumu S., Ishikawa T., Wakita T., Yoshioka K., Takayanagi M., Tahara H., Kusakabe A. Interferon-gamma production specific for hepatitis B virus antigen by intrahepatic T lymphocytes in patients with acute and chronic hepatitis B. Am J Gastroenterol. 1994 Jan;89(1):92–96. [PubMed] [Google Scholar]
  29. Kalams S. A., Johnson R. P., Trocha A. K., Dynan M. J., Ngo H. S., D'Aquila R. T., Kurnick J. T., Walker B. D. Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire. J Exp Med. 1994 Apr 1;179(4):1261–1271. doi: 10.1084/jem.179.4.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kita H., Moriyama T., Kaneko T., Harase I., Nomura M., Miura H., Nakamura I., Yazaki Y., Imawari M. HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein. Hepatology. 1993 Nov;18(5):1039–1044. [PubMed] [Google Scholar]
  31. Klenerman P., Rowland-Jones S., McAdam S., Edwards J., Daenke S., Lalloo D., Köppe B., Rosenberg W., Boyd D., Edwards A. Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants. Nature. 1994 Jun 2;369(6479):403–407. doi: 10.1038/369403a0. [DOI] [PubMed] [Google Scholar]
  32. Koziel M. J., Dudley D., Afdhal N., Choo Q. L., Houghton M., Ralston R., Walker B. D. Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. J Virol. 1993 Dec;67(12):7522–7532. doi: 10.1128/jvi.67.12.7522-7532.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Koziel M. J., Dudley D., Afdhal N., Grakoui A., Rice C. M., Choo Q. L., Houghton M., Walker B. D. HLA class I-restricted cytotoxic T lymphocytes specific for hepatitis C virus. Identification of multiple epitopes and characterization of patterns of cytokine release. J Clin Invest. 1995 Nov;96(5):2311–2321. doi: 10.1172/JCI118287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Koziel M. J., Dudley D., Wong J. T., Dienstag J., Houghton M., Ralston R., Walker B. D. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol. 1992 Nov 15;149(10):3339–3344. [PubMed] [Google Scholar]
  35. Missale G., Redeker A., Person J., Fowler P., Guilhot S., Schlicht H. J., Ferrari C., Chisari F. V. HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis. J Exp Med. 1993 Mar 1;177(3):751–762. doi: 10.1084/jem.177.3.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Moriyama T., Guilhot S., Klopchin K., Moss B., Pinkert C. A., Palmiter R. D., Brinster R. L., Kanagawa O., Chisari F. V. Immunobiology and pathogenesis of hepatocellular injury in hepatitis B virus transgenic mice. Science. 1990 Apr 20;248(4953):361–364. doi: 10.1126/science.1691527. [DOI] [PubMed] [Google Scholar]
  37. Müllbacher A., Lobigs M. Up-regulation of MHC class I by flavivirus-induced peptide translocation into the endoplasmic reticulum. Immunity. 1995 Aug;3(2):207–214. doi: 10.1016/1074-7613(95)90090-x. [DOI] [PubMed] [Google Scholar]
  38. Napoli J., Bishop G. A., McGuinness P. H., Painter D. M., McCaughan G. W. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines. Hepatology. 1996 Oct;24(4):759–765. doi: 10.1002/hep.510240402. [DOI] [PubMed] [Google Scholar]
  39. Nayersina R., Fowler P., Guilhot S., Missale G., Cerny A., Schlicht H. J., Vitiello A., Chesnut R., Person J. L., Redeker A. G. HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. J Immunol. 1993 May 15;150(10):4659–4671. [PubMed] [Google Scholar]
  40. Niewiesk S., Daenke S., Parker C. E., Taylor G., Weber J., Nightingale S., Bangham C. R. The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis. J Virol. 1994 Oct;68(10):6778–6781. doi: 10.1128/jvi.68.10.6778-6781.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rehermann B., Chang K. M., McHutchison J. G., Kokka R., Houghton M., Chisari F. V. Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection. J Clin Invest. 1996 Sep 15;98(6):1432–1440. doi: 10.1172/JCI118931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rehermann B., Ferrari C., Pasquinelli C., Chisari F. V. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med. 1996 Oct;2(10):1104–1108. doi: 10.1038/nm1096-1104. [DOI] [PubMed] [Google Scholar]
  43. Rehermann B., Fowler P., Sidney J., Person J., Redeker A., Brown M., Moss B., Sette A., Chisari F. V. The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J Exp Med. 1995 Mar 1;181(3):1047–1058. doi: 10.1084/jem.181.3.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rehermann B., Lau D., Hoofnagle J. H., Chisari F. V. Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest. 1996 Apr 1;97(7):1655–1665. doi: 10.1172/JCI118592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rehermann B., Pasquinelli C., Mosier S. M., Chisari F. V. Hepatitis B virus (HBV) sequence variation of cytotoxic T lymphocyte epitopes is not common in patients with chronic HBV infection. J Clin Invest. 1995 Sep;96(3):1527–1534. doi: 10.1172/JCI118191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Scaglioni P. P., Melegari M., Wands J. R. Posttranscriptional regulation of hepatitis B virus replication by the precore protein. J Virol. 1997 Jan;71(1):345–353. doi: 10.1128/jvi.71.1.345-353.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Shimizu Y. K., Hijikata M., Iwamoto A., Alter H. J., Purcell R. H., Yoshikura H. Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. J Virol. 1994 Mar;68(3):1494–1500. doi: 10.1128/jvi.68.3.1494-1500.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Thiers V., Nakajima E., Kremsdorf D., Mack D., Schellekens H., Driss F., Goudeau A., Wands J., Sninsky J., Tiollais P. Transmission of hepatitis B from hepatitis-B-seronegative subjects. Lancet. 1988 Dec 3;2(8623):1273–1276. doi: 10.1016/s0140-6736(88)92891-7. [DOI] [PubMed] [Google Scholar]
  49. Weiner A., Erickson A. L., Kansopon J., Crawford K., Muchmore E., Hughes A. L., Houghton M., Walker C. M. Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2755–2759. doi: 10.1073/pnas.92.7.2755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. de Campos-Lima P. O., Gavioli R., Zhang Q. J., Wallace L. E., Dolcetti R., Rowe M., Rickinson A. B., Masucci M. G. HLA-A11 epitope loss isolates of Epstein-Barr virus from a highly A11+ population. Science. 1993 Apr 2;260(5104):98–100. doi: 10.1126/science.7682013. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES