Association of NKG2A with treatment for chronic hepatitis C virus infection.

Abstract

Natural killer (NK) cells are critical to the immune response to viral infections. Their functions are controlled by receptors for major histocompatibility complex (MHC) class I, including NKG2A and killer-cell immunoglobulin-like receptors (KIR). In order to evaluate the role of MHC class I receptors in the immune response to hepatitis C virus infection we have studied patients with chronic HCV infection by multi-parameter flow cytometry directly ex vivo. This has permitted evaluation of combinatorial expression of activating and inhibitory receptors on single NK cells. Individuals with chronic HCV infection had fewer CD56(dim) NK cells than healthy controls (4.9 +/- 3.4% versus 9.0 +/- 5.9%, P < 0.05). Expression levels of the inhibitory receptor NKG2A was up-regulated on NK cells from individuals with chronic hepatitis C virus (HCV) (NKG2A mean fluorescence intensity 5692 +/- 2032 versus 4525 +/- 1646, P < 0.05). Twelve individuals were treated with pegylated interferon and ribavirin. This resulted in a down-regulation of NKG2A expression on CD56(dim) NK cells. Individuals with a sustained virological response (SVR) had greater numbers of NKG2A-positive, KIR-negative NK cells than those without SVR (27.6 +/- 9.6% NK cells versus 17.6 +/- 5.7, P < 0.02). Our data show that NKG2A expression is dysregulated in chronic HCV infection and that NKG2A-positive NK cells are associated with a beneficial response to pegylated interferon and ribavirin therapy.

• Authors: R J Harrison, A Ettorre, A-M Little, S I Khakoo
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 161 Issue 2 Pg. 306-14 (Aug 2010) ISSN: 1365-2249 [Electronic] England
• PMID: 20550548 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• CD3 Complex
• CD56 Antigen
• HLA Antigens
• Interferon alpha-2
• Interferon-alpha
• KLRC1 protein, human
• KLRK1 protein, human
• NCR1 protein, human
• NCR3 protein, human
• NK Cell Lectin-Like Receptor Subfamily C
• NK Cell Lectin-Like Receptor Subfamily K
• Natural Cytotoxicity Triggering Receptor 1
• Natural Cytotoxicity Triggering Receptor 3
• RNA, Viral
• Receptors, KIR
• Receptors, KIR2DL1
• Receptors, KIR2DL3
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2a

Topics

• Adult
• Antiviral Agents (pharmacology, therapeutic use)
• CD3 Complex (metabolism)
• CD56 Antigen (metabolism)
• Cell Count
• Female
• HLA Antigens (metabolism)
• Hepatitis C, Chronic (drug therapy, immunology)
• Humans
• Interferon alpha-2
• Interferon-alpha (pharmacology, therapeutic use)
• Killer Cells, Natural (cytology, drug effects, immunology, metabolism)
• Male
• Middle Aged
• NK Cell Lectin-Like Receptor Subfamily C (metabolism)
• NK Cell Lectin-Like Receptor Subfamily K (metabolism)
• Natural Cytotoxicity Triggering Receptor 1 (metabolism)
• Natural Cytotoxicity Triggering Receptor 3 (metabolism)
• Polyethylene Glycols (pharmacology, therapeutic use)
• RNA, Viral (blood)
• Receptors, KIR (metabolism)
• Receptors, KIR2DL1 (metabolism)
• Receptors, KIR2DL3 (metabolism)
• Recombinant Proteins
• Remission Induction
• Ribavirin (pharmacology, therapeutic use)
• T-Lymphocytes (drug effects, metabolism)
• Time Factors