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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00118355" target="_blank" >RIV/00216224:14740/20:00118355 - isvavai.cz</a>

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/all.14322" target="_blank" >https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/all.14322</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/all.14322" target="_blank" >10.1111/all.14322</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 alpha beta 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. Naive (CCR7+ CD45RA+) and memory (not naive) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 mu mol/L NiSO4., TCR alpha- and beta-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. Results Stimulation of PBMCs with NiSO4 induced CD154 expression on similar to 0.1% (mean) of naive and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased similar to 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 alpha-chain segment TRAV9-2 or a histidine in their alpha- or beta-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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 alpha beta 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. Naive (CCR7+ CD45RA+) and memory (not naive) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 mu mol/L NiSO4., TCR alpha- and beta-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. Results Stimulation of PBMCs with NiSO4 induced CD154 expression on similar to 0.1% (mean) of naive and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased similar to 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 alpha-chain segment TRAV9-2 or a histidine in their alpha- or beta-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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30225 - Allergy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Allergy

ISSN

0105-4538

e-ISSN

—

Svazek periodika

75

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

2574-2586

Kód UT WoS článku

000531897200001

EID výsledku v databázi Scopus

2-s2.0-85084483210