PMID- 19307785
OWN - NLM
STAT- MEDLINE
DCOM- 20090522
LR  - 20090324
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 87
IP  - 4
DP  - 2009 Feb 27
TI  - Evidence for Induced Expression of HLA Class II on Human Islets: Possible 
      Mechanism for HLA Sensitization in Transplant Recipients.
PG  - 500-6
LID - 10.1097/TP.0b013e318195fc33 [doi]
AB  - Recent reports have shown that islet transplant recipients develop antibodies 
      against donor human leukocyte antigen (HLA) class I and II. Because human islets 
      do not express HLA class II under normal conditions, mechanisms underlying 
      induction of the anti-class II response are unclear. We hypothesized that under 
      inflammatory conditions, islets will have induced expression of HLA class II 
      leading to sensitization. Isolated human islets were divided into two groups. 
      Group 1 was cultured at 37 degrees C as control; group 2 was cultured similarly 
      in presence of tumor necrosis factor alpha and interferon gamma. After treatment, 
      islets were analyzed for expression of HLA class II using real-time polymerase 
      chain reaction, immunofluorescence and flow cytometry. Furthermore, serum from an 
      islet transplant recipient who developed anti-class II antibody was tested by 
      flow cytometry for immunoglobulin (Ig) binding to cytokine-stimulated islets. 
      Real-time polymerase chain reaction analysis for gene transcripts of class II 
      transactivator, HLA-DRagr;, and HLA-DRbeta1 showed maximum 9.38-, 18.95-, and 
      46.5-fold increase, respectively in group 2 when compared with control at 24 hr. 
      Cytokine treatment increased HLA class II expression markedly on both alpha and 
      beta cells in islets as evidenced by fluorescent imaging and flow cytometric 
      analysis. When patient serum was analyzed by flow cytometry, both IgM and IgG 
      binding was observed in cytokine-treated, HLA class II matched islet cells alone. 
      We conclude that inflammation leads to induced expression of HLA class II on 
      transplanted islet cells potentially causing antidonor sensitization and 
      adversely impacting islet transplant outcomes.
FAU - Jackson, Andrew M
AU  - Jackson AM
AD  - Baylor Regional Transplant Institute, Baylor University Medical Center, Dallas, 
      TX, USA.
FAU - Connolly, John E
AU  - Connolly JE
FAU - Matsumoto, Shinichi
AU  - Matsumoto S
FAU - Noguchi, Hirofumi
AU  - Noguchi H
FAU - Onaca, Nicholas
AU  - Onaca N
FAU - Levy, Marlon F
AU  - Levy MF
FAU - Naziruddin, Bashoo
AU  - Naziruddin B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Culture Media)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DR7 Antigen)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Isoantigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 63231-63-0 (RNA)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Cells, Cultured
MH  - Culture Media
MH  - Flow Cytometry
MH  - Gene Expression Regulation/immunology
MH  - Glucagon-Secreting Cells/immunology
MH  - HLA Antigens/*immunology
MH  - HLA-DR Antigens/genetics
MH  - HLA-DR7 Antigen/genetics
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - *Immunization
MH  - Insulin-Secreting Cells/immunology
MH  - Interferon-gamma/pharmacology
MH  - Islets of Langerhans/cytology/*immunology
MH  - Islets of Langerhans Transplantation/*immunology
MH  - Isoantigens/blood
MH  - Polymerase Chain Reaction
MH  - RNA/genetics
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2009/03/25 09:00
MHDA- 2009/05/23 09:00
CRDT- 2009/03/25 09:00
PHST- 2009/03/25 09:00 [entrez]
PHST- 2009/03/25 09:00 [pubmed]
PHST- 2009/05/23 09:00 [medline]
AID - 00007890-200902270-00006 [pii]
AID - 10.1097/TP.0b013e318195fc33 [doi]
PST - ppublish
SO  - Transplantation. 2009 Feb 27;87(4):500-6. doi: 10.1097/TP.0b013e318195fc33.