Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Blood |
| Vol/bind | 109 |
| Udgave nummer | 8 |
| Sider (fra-til) | 3198-206 |
| Antal sider | 8 |
| ISSN | 0006-4971 |
| DOI | |
| Status | Udgivet - 2006 |
| Udgivet eksternt | Ja |
Bibliografisk note
Keywords: Antigens, CD3; Antigens, CD4; Antigens, CD8; B-Lymphocytes; Cell Line; Exons; Female; Gene Expression Regulation; Humans; Infant; Killer Cells, Natural; Multiprotein Complexes; Mutagenesis, Insertional; Receptors, Antigen, T-Cell; Retroviridae; Severe Combined Immunodeficiency; T-Lymphocytes; Transduction, GeneticAdgang til dokumentet
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T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex. / Roberts, Joseph L; Lauritsen, Jens Peter H; Cooney, Myriah; Parrott, Roberta E; Sajaroff, Elisa O; Win, Chan M; Keller, Michael D; Carpenter, Jeffery H; Carabana, Juan; Krangel, Michael S; Sarzotti, Marcella; Zhong, Xiao-Ping; Wiest, David L; Buckley, Rebecca H.
I: Blood, Bind 109, Nr. 8, 2006, s. 3198-206.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex
AU - Roberts, Joseph L
AU - Lauritsen, Jens Peter H
AU - Cooney, Myriah
AU - Parrott, Roberta E
AU - Sajaroff, Elisa O
AU - Win, Chan M
AU - Keller, Michael D
AU - Carpenter, Jeffery H
AU - Carabana, Juan
AU - Krangel, Michael S
AU - Sarzotti, Marcella
AU - Zhong, Xiao-Ping
AU - Wiest, David L
AU - Buckley, Rebecca H
N1 - Keywords: Antigens, CD3; Antigens, CD4; Antigens, CD8; B-Lymphocytes; Cell Line; Exons; Female; Gene Expression Regulation; Humans; Infant; Killer Cells, Natural; Multiprotein Complexes; Mutagenesis, Insertional; Receptors, Antigen, T-Cell; Retroviridae; Severe Combined Immunodeficiency; T-Lymphocytes; Transduction, Genetic
PY - 2006
Y1 - 2006
N2 - CD3zeta is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T(-)B(+)NK(+) severe combined immunodeficiency (SCID) who was homozygous for a single C insertion following nucleotide 411 in exon 7 of the CD3zeta gene. The few T cells present contained no detectable CD3zeta protein, expressed low levels of cell surface CD3epsilon, and were nonfunctional. CD4(+)CD8(-)CD3epsilon(low), CD4(-)CD8(+)CD3epsilon(low), and CD4(-)CD8(-)CD3epsilon(low) cells were detected in the periphery, and the patient also exhibited an unusual population of CD56(-)CD16(+) NK cells with diminished cytolytic activity. Additional studies demonstrated that retrovirally transduced patient mutant CD3zeta cDNA failed to rescue assembly of nascent complete TCR complexes or surface TCR expression in CD3zeta-deficient MA5.8 murine T-cell hybridoma cells. Nascent transduced mutant CD3zeta protein was also not detected in metabolically labeled MA5.8 cells, suggesting that it was unstable and rapidly degraded. Taken together, these findings provide the first demonstration that complete CD3zeta deficiency in humans can cause SCID by preventing normal TCR assembly and surface expression.
AB - CD3zeta is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T(-)B(+)NK(+) severe combined immunodeficiency (SCID) who was homozygous for a single C insertion following nucleotide 411 in exon 7 of the CD3zeta gene. The few T cells present contained no detectable CD3zeta protein, expressed low levels of cell surface CD3epsilon, and were nonfunctional. CD4(+)CD8(-)CD3epsilon(low), CD4(-)CD8(+)CD3epsilon(low), and CD4(-)CD8(-)CD3epsilon(low) cells were detected in the periphery, and the patient also exhibited an unusual population of CD56(-)CD16(+) NK cells with diminished cytolytic activity. Additional studies demonstrated that retrovirally transduced patient mutant CD3zeta cDNA failed to rescue assembly of nascent complete TCR complexes or surface TCR expression in CD3zeta-deficient MA5.8 murine T-cell hybridoma cells. Nascent transduced mutant CD3zeta protein was also not detected in metabolically labeled MA5.8 cells, suggesting that it was unstable and rapidly degraded. Taken together, these findings provide the first demonstration that complete CD3zeta deficiency in humans can cause SCID by preventing normal TCR assembly and surface expression.
U2 - 10.1182/blood-2006-08-043166
DO - 10.1182/blood-2006-08-043166
M3 - Journal article
C2 - 17170122
VL - 109
SP - 3198
EP - 3206
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -