2013, Number 4
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Ann Hepatol 2013; 12 (4)
High frequencies of CD158b+ NK cells are associated with persistent hepatitis C virus infections
Hui-Fan J, Wang J, Lei Y, Jun-Qi N, Desalegn AA, Yan-Fang J
Language: English
References: 30
Page: 371-379
PDF size: 352.86 Kb.
ABSTRACT
Background. During the early phases of a hepatitis C virus (HCV) infection, NK cell activation appears to be
critical to the induction of adaptive immune responses that have the potential of clearing the infection.
This study aimed to investigate the phenotype and function of NK cells in chronic HCV (CHC) patients, particularly
patients who cleared HCV infections spontaneously (SR-HCV).
Material and methods. Peripheral
blood NK cells were compared between 36 CHC patients, 12 SR-HCV patients, and 14 healthy controls (HC).
The phenotype and function of NK cells were characterized by flow cytometry. In addition, the potential
associations between the frequency of NK cell subsets and ALT, AST and HCV viral loads were also analyzed.
Results. Our data revealed that the population of CD3-CD56
+ NK cells was significantly decreased in
CHC and SR-HCV patients compared to levels in HC (P = 0.031, P = 0.014). Interestingly, we found that the
levels of the CD158b inhibitory receptor were higher in CHC patients compared to levels observed in HC
and SR-HCV subjects (P = 0.018, P = 0.036). In addition, the percentages of the activation receptors
NKp30 and NKp46 were significantly decreased in CHC and SR-HCV patients compared to their expression
levels in HC (P ‹ 0.05). Moreover, the frequencies of inducible CD107a (but not IFN-γ-secreting) NK cells
from both CHC and SR-HCV patients were significantly lower than frequencies observed in controls
(P = 0.018, P = 0.027).
Conclusion. Our data indicated that the higher frequency of inhibitory NK cells
combined with fewer activated NK cells may be associated with HCV-related chronic inflammation
involved in CHC pathogenesis.
REFERENCES
Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, Cheng J, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 2004; 305: 872-4.
Cooper S, Erickson AL, Adams EJ, Kansopon J, Weiner AJ, Chien DY, Houghton M, et al. Analysis of a successful immune response against hepatitis C virus. Immunity 1999; 10: 439-49.
Lechner F, Wong DK, Dunbar PR, Chapman R, Chung RT, Dohrenwend P, Robbins G, et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 2000; 191: 1499-512.
Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 2001; 194: 1395-406.
Wieland SF, Chisari FV. Stealth and cunning: hepatitis B and hepatitis C viruses. J Virol 2005; 79: 9369-80.
Colucci F, Caligiuri MA, Di Santo JP. What does it take to make a natural killer? Nat Rev Immunol 2003; 3: 413-25.
Johansson S, Berg L, Hall H, Hoglund P. NK cells: elusive players in autoimmunity. Trends Immunol 2005; 26: 613-8.
Ahmad A, Alvarez F. Role of NK and NKT cells in the immunopathogenesis of HCV-induced hepatitis. J Leukoc Biol 2004; 76: 743-59.
Lanier LL. Activating and inhibitory NK cell receptors. Adv Exp Med Biol 1998; 452: 13-8.
Biron CA, Brossay L. NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol 2001; 13: 458-64.
Moretta L, Moretta A. Unravelling natural killer cell function: triggering and inhibitory human NK receptors. EMBO J 2004; 23: 255-9.
Biron CA. Activation and function of natural killer cell responses during viral infections. Curr Opin Immunol 1997; 9: 24-34.
Bozzano F, Picciotto A, Costa P, Marras F, Fazio V, Hirsch I, Olive D, et al. Activating NK cell receptor expression/ function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment. Eur J Immunol 2011; 41: 2905-14.
Corado J, Toro F, Rivera H, Bianco NE, Deibis L, De Sanctis JB. Impairment of natural killer (NK) cytotoxic activity in hepatitis C virus (HCV) infection. Clin Exp Immunol 1997; 109: 451-7.
Golden-Mason L, Rosen HR. Natural killer cells: primary target for hepatitis C virus immune evasion strategies? Liver Transpl 2006; 12: 363-72.
Sherman M, Shafran S, Burak K, Doucette K, Wong W, Girgrah N, Yoshida E, et al. Management of chronic hepatitis C: consensus guidelines. Can J Gastroenterol 2007; 21(Suppl. C): 25C-34C.
Sarasin-Filipowicz M. Interferon therapy of hepatitis C: molecular insights into success and failure. Swiss Med Wkly 2010; 140: 3-11.
Jiang Y, Ma Z, Xin G, Yan H, Li W, Xu H, Hao C, et al. Th1 and Th2 immune response in chronic hepatitis B patients during a long-term treatment with adefovir dipivoxil. Mediators Inflamm 2010; 2010: 143026.
Rehermann B, Naoumov NV. Immunological techniques in viral hepatitis. J Hepatol 2007; 46: 508-20.
Golden-Mason L, Madrigal-Estebas L, McGrath E, Conroy MJ, Ryan EJ, Hegarty JE, O’Farrelly C, et al. Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure. Gut 2008: 1121-8.
Morishima C, Paschal DM, Wang CC, Yoshihara CS, Wood BL, Yeo AE, Emerson SS, et al. Decreased NK cell frequency in chronic hepatitis C does not affect ex vivo cytolytic killing. Hepatology 2006; 43: 573-80.
Bonorino P, Ramzan M, Camous X, Dufeu-Duchesne T, Thelu MA, Sturm N, Dariz A, et al. Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C. J Hepatol 2009; 51: 458-67.
Nattermann J, Feldmann G, Ahlenstiel G, Langhans B, Sauerbruch T, Spengler U. Surface expression and cytolytic function of natural killer cell receptors is altered in chronic hepatitis C. Gut 2006; 55: 869-87.
Biassoni R, Cantoni C, Falco M, Verdiani S, Bottino C, Vitale M, Conte R, et al. The human leukocyte antigen (HLA)-Cspecific “activatory” or “inhibitory” natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions. J Exp Med 1996; 183: 645-50.
Wagtmann N, Biassoni R, Cantoni C, Verdiani S, Malnati MS, Vitale M, Bottino C, et al. Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity 1995; 2: 439-49.
Velardi A. Role of KIRs and KIR ligands in hematopoietic transplantation. Curr Opin Immunol 2008; 20: 581-7.
Guerra N, Guillard M, Angevin E, Echchakir H, Escudier B, Moretta A, Chouaib S, et al. Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas. Blood 2000; 95: 2883-9.
Golden-Mason L, Bambha KM, Cheng L, Howell CD, Taylor MW, Clark PJ, Afdhal N, et al. Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C. Hepatology 2011; 54: 1559-69.
Solerte SB, Cravello L, Ferrari E, Fioravanti M. Overproduction of IFN-gamma and TNF-alpha from natural killer (NK) cells is associated with abnormal NK reactivity and cognitive derangement in Alzheimer’s disease. Ann N Y Acad Sci 2000; 917: 331-40.
Pelletier S, Drouin C, Bedard N, Khakoo SI, Bruneau J, Shoukry NH. Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virusspecific T cell responses. J Hepatol 2010; 53: 805-16.