Impaired cell surface expression of HLA-B antigens on mesenchymal stem cells and muscle cell progenitors

Adiba Isa, Jan Nehlin, Hardee Jawad Sabir, Tom Andersen, Michael Gaster, Moustapha Kassem, Torben Barington

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC) using relevant human anti-B and anti-Cw sera. IFNgamma stimulation for 48-72 h was required to induce full HLA-B protein expression. Quantitative real-time RT-PCR showed that IFNgamma induced a 9-42 fold increase of all six HLA-A,-B,-C gene transcripts. Interestingly, prior to stimulation, gene transcripts for all but two alleles were present in similar amounts suggesting that post-transcriptional mechanisms regulate the constitutive expression of HLA-A,-B, and -C. Locus-restricted expression of HLA-A, -B and -C challenges our current understanding of the function of these molecules as regulators of CD8(+) T-cell and NK-cell function and should lead to further inquiries into their expression on other cell types.
OriginalsprogEngelsk
TidsskriftP L o S One
Vol/bind5
Udgave nummer5
Sider (fra-til)e10900
ISSN1932-6203
DOI
StatusUdgivet - 2010

Fingeraftryk

HLA-A Antigens
HLA-B Antigens
Stem cells
Mesenchymal Stromal Cells
myocytes
Muscle
stem cells
Cells
antigens
alleles
striated muscle
embryonic stem cells
natural killer cells
cells
mononuclear leukocytes
bone marrow
Genes
adipose tissue
flow cytometry
antiserum

Citer dette

Isa, Adiba ; Nehlin, Jan ; Sabir, Hardee Jawad ; Andersen, Tom ; Gaster, Michael ; Kassem, Moustapha ; Barington, Torben. / Impaired cell surface expression of HLA-B antigens on mesenchymal stem cells and muscle cell progenitors. I: P L o S One. 2010 ; Bind 5, Nr. 5. s. e10900.
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abstract = "HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC) using relevant human anti-B and anti-Cw sera. IFNgamma stimulation for 48-72 h was required to induce full HLA-B protein expression. Quantitative real-time RT-PCR showed that IFNgamma induced a 9-42 fold increase of all six HLA-A,-B,-C gene transcripts. Interestingly, prior to stimulation, gene transcripts for all but two alleles were present in similar amounts suggesting that post-transcriptional mechanisms regulate the constitutive expression of HLA-A,-B, and -C. Locus-restricted expression of HLA-A, -B and -C challenges our current understanding of the function of these molecules as regulators of CD8(+) T-cell and NK-cell function and should lead to further inquiries into their expression on other cell types.",
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Impaired cell surface expression of HLA-B antigens on mesenchymal stem cells and muscle cell progenitors. / Isa, Adiba; Nehlin, Jan; Sabir, Hardee Jawad; Andersen, Tom; Gaster, Michael; Kassem, Moustapha; Barington, Torben.

I: P L o S One, Bind 5, Nr. 5, 2010, s. e10900.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Impaired cell surface expression of HLA-B antigens on mesenchymal stem cells and muscle cell progenitors

AU - Isa, Adiba

AU - Nehlin, Jan

AU - Sabir, Hardee Jawad

AU - Andersen, Tom

AU - Gaster, Michael

AU - Kassem, Moustapha

AU - Barington, Torben

PY - 2010

Y1 - 2010

N2 - HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC) using relevant human anti-B and anti-Cw sera. IFNgamma stimulation for 48-72 h was required to induce full HLA-B protein expression. Quantitative real-time RT-PCR showed that IFNgamma induced a 9-42 fold increase of all six HLA-A,-B,-C gene transcripts. Interestingly, prior to stimulation, gene transcripts for all but two alleles were present in similar amounts suggesting that post-transcriptional mechanisms regulate the constitutive expression of HLA-A,-B, and -C. Locus-restricted expression of HLA-A, -B and -C challenges our current understanding of the function of these molecules as regulators of CD8(+) T-cell and NK-cell function and should lead to further inquiries into their expression on other cell types.

AB - HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC) using relevant human anti-B and anti-Cw sera. IFNgamma stimulation for 48-72 h was required to induce full HLA-B protein expression. Quantitative real-time RT-PCR showed that IFNgamma induced a 9-42 fold increase of all six HLA-A,-B,-C gene transcripts. Interestingly, prior to stimulation, gene transcripts for all but two alleles were present in similar amounts suggesting that post-transcriptional mechanisms regulate the constitutive expression of HLA-A,-B, and -C. Locus-restricted expression of HLA-A, -B and -C challenges our current understanding of the function of these molecules as regulators of CD8(+) T-cell and NK-cell function and should lead to further inquiries into their expression on other cell types.

KW - Alleles

KW - Cell Membrane

KW - Cytotoxicity, Immunologic

KW - Down-Regulation

KW - Flow Cytometry

KW - Gene Expression Regulation

KW - HLA-A Antigens

KW - HLA-B Antigens

KW - HLA-C Antigens

KW - Humans

KW - Interferon-gamma

KW - Intracellular Space

KW - Kinetics

KW - Mesenchymal Stem Cells

KW - RNA, Messenger

KW - Satellite Cells, Skeletal Muscle

U2 - 10.1371/journal.pone.0010900

DO - 10.1371/journal.pone.0010900

M3 - Journal article

C2 - 20531935

VL - 5

SP - e10900

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 5

ER -