Interferon therapy shifts natural killer subsets among Egyptian patients with chronic hepatitis C

Fathy, Amal; Eldin, Mohamed Mohy; Metwally, Lobna; Eida, Mohamed; Abdel-Rehim, Marwa; Esmat, Gamal

doi:10.1016/S1413-8670(10)70082-9

Article information

Abstract

Bibliography

Download PDF

Statistics

Abstract

Natural killer cells can be divided into five subpopulations based on the relative expression of CD16 and CD56 markers. The majority of natural killer cells are CD56dim, which are considered to be the main cytotoxic effectors. A minority of the natural killer cells are CD56bright, and function as an important source of immune-regulatory cytokines. Shifts of these subsets have been reported in patients with chronic hepatitis C virus infection. We sought to investigate the shift of natural killer subsets among Egyptian patients with chronic HCV and to analyze the influence of interferon therapy on this shift. We applied a flow cytometric analysis of peripheral blood natural killer subsets for 12 interferon-untreated and 12 interferon-treated patients with chronic HCV, in comparison to 10 control subjects. Among interferon-untreated patients, there was a significant reduction of CD56-16+ (immature natural killer) cells. Among interferon-treated patients, the absolute count of natural killer cells was reduced, with expansion of the CD56bright subset and reduction of the CD56dim16+ subset. Natural killer subset counts were not significantly correlated to HCV viral load and were not significantly different among interferon responders and non-responders. In conclusion, HCV infection in Egyptian patients has been observed to be statistically and significantly associated with reduction of the CD56-16+NK subset, while a statistically significant expansion of CD56bright and reduction of CD56dim16+ subsets were observed after interferon therapy. Further studies are required to delineate the molecular basis of interferon-induced shift of natural killer subsets among patients with HCV.

Keywords:

natural killer cells

natural killer subsets

chronic hepatitis C

innate immunity

interferon

Full text is only aviable in PDF

References

[1.]

W.M. Yokoyama.

Natural killer cell receptors.

Current Opinion Immunology, 10 (1998), pp. 298-305

[2.]

T. Timonen.

Natural killer cells: Endothelial interactions, migration, and target cell recognition.

J Leukocyte Biology, 62 (1997), pp. 693-701

[3.]

B. Rolstad, W.E. Seaman.

Natural killer cells and recognition of MHC class I molecules: New perspectives and challenges in immunology.

Scand J Immunology, 47 (1998), pp. 412-425

[4.]

M.J. Robertson, C. Cameron, S. Lazo, et al.

Costimulation of human natural killer cell proliferation: Role of accessory cytokines and cell contact-dependent signals.

Natural Immunity, 15 (1996), pp. 213-226

Medline

[5.]

J.H. Phillips, L.L. Lanier.

Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis.

J Exp Medicine, 164 (1986), pp. 814-825

[6.]

J. OShea, J.R. Ortaldo.

The biology of natural killer cells: insights into the molecular basis of function.

The Natural Immune System. The Natural Killer Cell,

[7.]

G. Trinchieri.

Biology of natural killer cells.

Adv Immunol, 47 (1998), pp. 187-376

Medline

[8.]

M.A. Cooper, T.A. Fehniger, M.A. Caligiuri.

The biology of human natural killer-cell subsets.

Trends Immunol, 22 (2001), pp. 633-640

Medline

[9.]

M. Caligiuri.

Human natural killer cells.

Blood, 112 (2008), pp. 461-469

http://dx.doi.org/10.1182/blood-2007-09-077438 | Medline

[10.]

J. Cohen.

The scientific challenge of hepatitis C.

Science, 285 (1999), pp. 26-30

Medline

[11.]

M.J. Tong, N.S. El-Farra, A.R. Reikes, R.L. Co.

Clinical outcomes after transfusion-associated hepatitis C.

N Engl J Med, 332 (1995), pp. 1463-1466

http://dx.doi.org/10.1056/NEJM199506013322202 | Medline

[12.]

T.P. Salazar-Mather, J.S. Orange, C.A. Biron.

Early murine cytomegalovirus (MCMV) infection induces liver natural killer (NK) cell inflammation and protection through macrophage inflammatory protein 1α (MIP-1α)-dependent pathways.

J Exp Med, 187 (1998), pp. 1-14

Medline

[13.]

Z.X. Liu, S. Govindarajan, S. Okamoto, G. Dennert.

NK cells cause liver injury and facilitate the induction of T cell-mediated immunity to a viral liver infection.

J Immunol, 164 (2000), pp. 6480-6486

Medline

[14.]

Li Y, Zhang T, Ho C et al. Natural killer cells inhibit hepatitis C virus replicon expression mediated by interferon. 8th Annual Meeting of the Society for Natural Immunity, Noordwijkerhout, the Netherlands; Abstract No. C035, Abstract Book, 54, 2004.

[15.]

M. Thomson, M. Nascimbeni, M.B. Havert, et al.

The clearance of hepatitis C virus infection in chimpanzees may not necessarily correlate with the appearance of acquired immunity.

J Virol, 77 (2003), pp. 862-870

Medline

[16.]

N.H. Shoukry, A. Grakoui, M. Houghton, et al.

Memory CD8 T cells are required for protection from persistent hepatitis C virus infection.

J Exp Med, 197 (2003), pp. 1645-1655

http://dx.doi.org/10.1084/jem.20030239 | Medline

[17.]

U.C. Meier, R.E. Owen, E. Taylor, et al.

Shared Alterations in NK Cell Frequency. Phenotype, and Function in Chronic Human Immunodeficiency Virus and Hepatitis C Virus Infections.

J Virol, 19 (2005), pp. 12365-12374

[18.]

K.G. Ishak.

Chronic hepatitis: Morphology and nomenclature.

Mod Pathol, 7 (1994), pp. 690-713

Medline

[19.]

H. Arase, N. Arase, T. Saito.

Fas-mediated cytotoxicity by freshly isolated natural killer cells.

J Exp Med, 181 (1995), pp. 1235-1238

Medline

[20.]

L. Zamai, M. Ahmad, I.M. Bennett, et al.

Natural killer (NK) cell-mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells.

J Exp Med, 188 (1998), pp. 2375-2380

Medline

[21.]

H.J. van der Vliet, B.M. von Blomberg, M.D. Hazenberg, et al.

Selective decrease in circulating V alpha 24 + V beta 11 + NKT cells during HIV type 1 infection.

J Immunol, 168 (2002), pp. 1490-1495

Medline

[22.]

L.G. Guidotti, F.V. Chisari.

Noncytolytic control of viral infections by the innate and adaptive immune response.

Annu Rev Immunol, 19 (2001), pp. 65-91

http://dx.doi.org/10.1146/annurev.immunol.19.1.65 | Medline

[23.]

V.D. Gonzalez, K. Falconer, J. Michaëlsson, et al.

Expansion of CD56- NK cells in chronic HCV/HIV-1 coinfection: reversion by antiviral treatment with pegylated IFN-alpha and ribavirin.

Clin Immunol, 1 (2008), pp. 46-56

[24.]

M.A. Zarife, E.A. Reis, T.M. Carmo, et al.

Increased frequency of CD56 Bright NK-cells. CD3-CD16+CD56-NK-cells and activated CD4+T-cells or B-cells in parallel with CD4+CD25High T-cells control potentially viremia in blood donors with HCV.

J Med Virol, 81 (2009), pp. 49-59

http://dx.doi.org/10.1002/jmv.21340 | Medline

[25.]

A. el-Zayadi, P. Simmonds, H. Dabbous, et al.

Response to interferon-alpha of Egyptian patients infected with hepatitis C virus genotype 4.

J Viral Hepat, 3 (1996), pp. 261-264

Medline

[26.]

M. Saraste, H. Irjala, L. Airas.

Expansion of CD56bright natural killer cells in the peripheral blood of multiple sclerosis patients treated with interferon-beta.

Neurol Sci, 28 (2007), pp. 121-126

http://dx.doi.org/10.1007/s10072-007-0803-3 | Medline

[27.]

W. Carson, M. Caligiuri.

Natural killer cell subsets and development.

Methods, 9 (1996), pp. 327-343

Medline

[28.]

A. Panasiuk, D. Prokopowicz, J. Zak.

Immunological response in chronic hepatitis C virus infection during interferon alpha therapy.

Hepatogastroenterology, 58 (2004), pp. 1088-1092

[29.]

S.I. Khakoo, C.L. Thio, M.P. Martin, et al.

HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.

Science, 305 (2004), pp. 872-874

http://dx.doi.org/10.1126/science.1097670 | Medline

[30.]

A.W. Lin, S.A. Gonzalez, S. Cunningham-Rundles, et al.

CD56+dim and CD56+bright cell activation and apoptosis in hepatitis C virus infection.

Clin Exp Immunol, 137 (2004), pp. 408-416

http://dx.doi.org/10.1111/j.1365-2249.2004.02523.x | Medline

[31.]

R. Jacobs, G. Hintzen, A. Kemper, et al.

CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells.

Eur J Immunol, 31 (2001), pp. 3121-3127

http://dx.doi.org/10.1002/1521-4141(2001010)31:10<3121::AID-IMMU3121>3.0.CO;2-4 | Medline

[32.]

M. Pernollet, E. Jouvin-Marche, V. Leroy, et al.

Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions.

Clin Exp Immunol, 130 (2002), pp. 518-525

Medline

Indexed in:

Follow us:

Indexed in:

Follow us:

Subscribe to our newsletter