PMID- 17559153
OWN - NLM
STAT- MEDLINE
DCOM- 20070830
LR  - 20140729
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 46
IP  - 2
DP  - 2007 Aug
TI  - Cytochrome P450IID6-specific CD8 T cell immune responses mirror disease activity 
      in autoimmune hepatitis type 2.
PG  - 472-84
AB  - Autoimmune hepatitis type 2 (AIH-2) is a severe organ-specific disorder 
      characterized by liver kidney microsomal antibody type 1 targeting cytochrome 
      P4502D6 (CYP2D6). Growing evidence implicates the involvement of CD8 T cell 
      immune responses in its pathogenesis. We investigated CYP2D6-specific CD8 T cell 
      human leukocyte antigen (HLA)-A2 restricted responses in AIH-2 (20 patients, 11 
      HLA-A2+). Binding affinity of CYP2D6 peptides to HLA-A2 was predicted by the 
      algorithm SYFPEITHI and assessed in vivo by T2 cell assays. CD8 T cell interferon 
      (IFN)-gamma production was assessed via intracellular cytokine staining, 
      cytotoxicity via chromium release assay, and frequency of circulating and 
      intrahepatic CYP2D6-specific CD8 T cells via tetramer staining. CYP2D6-specific 
      CD8 T cell reactivity was tested at diagnosis and during treatment and correlated 
      with indices of disease activity. Seven CYP2D6 peptides with high HLA-A2 binding 
      affinity colocalizing with known B cell or CD4 T cell epitopes were selected. 
      Five sequences inducing high levels of IFN-gamma were used for HLA-A2 tetramer 
      construction. Frequency, IFN-gamma production, and cytotoxicity of 
      CYP2D6-specific CD8 T cells were higher at diagnosis than during treatment. 
      Intensity of CYP2D6-specific CD8 T cell responses correlated with disease 
      activity. Immune responses to CYP2D6(245-254) were the strongest both at 
      diagnosis and during treatment. CONCLUSION: HLA-A2-restricted, CYP2D6-specific 
      CD8 T cell immune responses vary according to disease stage and correlate with 
      hepatocyte damage. CD8 T cell targets on CYP2D6-in particular CYP2D6(245-254)-may 
      be the focus of novel immune intervention in AIH-2. (HEPATOLOGY 2007.).
FAU - Longhi, Maria Serena
AU  - Longhi MS
AD  - Institute of Liver Studies, King's College London School of Medicine at King's 
      College Hospital, Denmark Hill, London, UK.
FAU - Hussain, Munther J
AU  - Hussain MJ
FAU - Bogdanos, Dimitrios P
AU  - Bogdanos DP
FAU - Quaglia, Alberto
AU  - Quaglia A
FAU - Mieli-Vergani, Giorgina
AU  - Mieli-Vergani G
FAU - Ma, Yun
AU  - Ma Y
FAU - Vergani, Diego
AU  - Vergani D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA-A2 Antigen)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
SB  - IM
CIN - Hepatology. 2008 Jun;47(6):2147-8. PMID: 18459130
MH  - Adolescent
MH  - Adult
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Child
MH  - Child, Preschool
MH  - Cytochrome P-450 CYP2D6/*immunology
MH  - Cytotoxicity, Immunologic
MH  - Female
MH  - HLA-A2 Antigen/analysis/immunology
MH  - Hepatitis, Autoimmune/*immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - Interferon-gamma/biosynthesis
MH  - Male
EDAT- 2007/06/15 09:00
MHDA- 2007/08/31 09:00
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2007/08/31 09:00 [medline]
PHST- 2007/06/15 09:00 [entrez]
AID - 10.1002/hep.21658 [doi]
PST - ppublish
SO  - Hepatology. 2007 Aug;46(2):472-84. doi: 10.1002/hep.21658.