Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+ T cells

M. Aparicio-Soto, F. Riedel, M. Leddermann, P. Bacher, A. Scheffold, H. Kuhl, B. Timmermann, DM. Chudakov, S. Molin, M. Worm, G. Heine, HJ. Thierse, A. Luch, K. Siewert

. 2020 ; 75 (10) : 2574-2586. [pub] 20200513

Jazyk angličtina Země Dánsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21020015

BACKGROUND: Nickel is the most frequent cause of T cell-mediated allergic contact dermatitis worldwide. In vitro, CD4+ T cells from all donors respond to nickel but the involved αβ T cell receptor (TCR) repertoire has not been comprehensively analyzed. METHODS: We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel-specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Naïve (CCR7+ CD45RA+) and memory (not naïve) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 µmol/L NiSO4 ., TCR α- and β-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. RESULTS: Stimulation of PBMCs with NiSO4 induced CD154 expression on ~0.1% (mean) of naïve and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased ~13-fold and were associated with markers of in vivo activation. CD154 expression was TCR-mediated since single clones could be specifically restimulated. Among nickel-specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the α-chain segment TRAV9-2 or a histidine in their α- or β-chain complementarity determining region 3 (CDR3) were highly overrepresented. CONCLUSIONS: Induced CD154 expression represents a reliable method to study nickel-specific CD4+ T cells. TCRs with particular features respond in all donors, while strongly increased blood frequencies indicate nickel allergy for some donors. Our approach may be extended to other contact allergens for the further development of diagnostic and predictive in vitro tests.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21020015
003      
CZ-PrNML
005      
20210830101623.0
007      
ta
008      
210728s2020 dk f 000 0|eng||
009      
AR
024    7_
$a 10.1111/all.14322 $2 doi
035    __
$a (PubMed)32298488
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a dk
100    1_
$a Aparicio-Soto, Marina $u Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany
245    10
$a TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+ T cells / $c M. Aparicio-Soto, F. Riedel, M. Leddermann, P. Bacher, A. Scheffold, H. Kuhl, B. Timmermann, DM. Chudakov, S. Molin, M. Worm, G. Heine, HJ. Thierse, A. Luch, K. Siewert
520    9_
$a BACKGROUND: Nickel is the most frequent cause of T cell-mediated allergic contact dermatitis worldwide. In vitro, CD4+ T cells from all donors respond to nickel but the involved αβ T cell receptor (TCR) repertoire has not been comprehensively analyzed. METHODS: We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel-specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Naïve (CCR7+ CD45RA+) and memory (not naïve) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 µmol/L NiSO4 ., TCR α- and β-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. RESULTS: Stimulation of PBMCs with NiSO4 induced CD154 expression on ~0.1% (mean) of naïve and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased ~13-fold and were associated with markers of in vivo activation. CD154 expression was TCR-mediated since single clones could be specifically restimulated. Among nickel-specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the α-chain segment TRAV9-2 or a histidine in their α- or β-chain complementarity determining region 3 (CDR3) were highly overrepresented. CONCLUSIONS: Induced CD154 expression represents a reliable method to study nickel-specific CD4+ T cells. TCRs with particular features respond in all donors, while strongly increased blood frequencies indicate nickel allergy for some donors. Our approach may be extended to other contact allergens for the further development of diagnostic and predictive in vitro tests.
650    _2
$a CD4-pozitivní T-lymfocyty $7 D015496
650    12
$a hypervariabilní oblasti $7 D022801
650    _2
$a histidin $7 D006639
650    12
$a nikl $7 D009532
650    _2
$a náplasťové testy $7 D010328
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Riedel, Franziska $u Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany
700    1_
$a Leddermann, Melanie $u Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany
700    1_
$a Bacher, Petra $u Institute of Immunology, Christian-Albrechts Universität zu Kiel and Universitätsklinik Schleswig-Holstein, Kiel, Germany $u Institute of Clinical Molecular Biology, Christian-Albrechts Universität zu Kiel, Kiel, Germany
700    1_
$a Scheffold, Alexander $u Institute of Immunology, Christian-Albrechts Universität zu Kiel and Universitätsklinik Schleswig-Holstein, Kiel, Germany
700    1_
$a Kuhl, Heiner $u Sequencing Core Facility, Max-Planck-Institute of Molecular Genetics, Berlin, Germany
700    1_
$a Timmermann, Bernd $u Sequencing Core Facility, Max-Planck-Institute of Molecular Genetics, Berlin, Germany
700    1_
$a Chudakov, Dmitriy M $u Genomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia $u Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russia $u Center of Molecular Medicine, CEITEC, Masaryk University, Brno, Czech Republic
700    1_
$a Molin, Sonja $u Division of Dermatology, Queen's University, Kingston, ON, Canada $u Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany
700    1_
$a Worm, Margitta $u Division of Allergy and Immunology, Department of Dermatology, Venerology, and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany
700    1_
$a Heine, Guido $u Division of Allergy and Immunology, Department of Dermatology, Venerology, and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany $u Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany
700    1_
$a Thierse, Hermann-Josef $u Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany
700    1_
$a Luch, Andreas $u Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany
700    1_
$a Siewert, Katherina $u Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany
773    0_
$w MED00009088 $t Allergy $x 1398-9995 $g Roč. 75, č. 10 (2020), s. 2574-2586
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32298488 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210728 $b ABA008
991    __
$a 20210830101623 $b ABA008
999    __
$a ok $b bmc $g 1690746 $s 1140461
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 75 $c 10 $d 2574-2586 $e 20200513 $i 1398-9995 $m Allergy $n Allergy $x MED00009088
LZP    __
$a Pubmed-20210728

Najít záznam

Citační ukazatele

Možnosti archivace