Identification and Characterization of Circulating Naïve CD4+ and CD8+ T Cells Recognizing Nickel

Bechara, Rami; Pollastro, Sabrina; Azoury, Marie Eliane; Szely, Natacha; Maillère, Bernard; Vries, Niek de; Pallardy, Marc

doi:10.3389/fimmu.2019.01331

Cited by 14 publications

(24 citation statements)

References 54 publications

(80 reference statements)

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“…This technique is being increasingly used to identify pathogenic T cells in many different immune-mediated diseases [ 28 , 29 ]. In this study, we showed several highly expanded T cell clones by sequencing data, and demonstrated the preferential usage of TRBV19, TRBV5-1, and TRBV20-1, consistent with previous studies on Ni 2+ contact dermatitis [ 11 , 16 , 18 , 20 ]. Our study suggests, then, that the certain population of Ni 2+ -reactive T cells in joint implant failure may be shared with the T cells responsible for Ni 2+ induced contact dermatitis.…”

Section: Discussionsupporting

confidence: 91%

“…The ternary structure of the ANi2.3 TCR, MHC and mimotope confirmed that Ni 2+ presentation required both a specific MHC and peptides [ 15 ]. Recently, a study by Bechara et al also showed the dominant usage of TRBV19 in highly expanded clones from Ni 2+ -specific naive T cell lines derived from Ni 2+ sensitized contact dermatitis subjects [ 16 ]. However, another paper found dominant usage of TRAV9-2 rather than TRBV19 in CD154 positive nickel-stimulated T cells [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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The T Cell Repertoires from Nickel Sensitized Joint Implant Failure Patients

Chen

Zhang

Pacheco

et al. 2021

IJMS

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Nickel (Ni2+) is one of the most common allergens, affecting around 10–15% of the general population. As the demand for orthopedic implant surgery rises, the number of surgical revisions due to joint implant failure also increases. There is evidence that some patients develop joint failure due to an immune response to a component of the implant, and we have found that Ni2+ is an especially important cause. Hence, understanding the mechanisms by which Ni2+ allergy induces joint implant failure becomes a critical research question. The structural basis of Ni2+ activation of pathogenic T cells is still not clear. The purpose of this study was to characterize Ni2+-reactive T cell repertoires derived from the peripheral blood of joint failure patients due to Ni2+ sensitization using single-cell sequencing techniques. We stimulated the proliferation of Ni2+ -reactive T cells from two implant failure patients in vitro, and sorted them for single-cell VDJ sequencing (10× genomics). We identified 2650 productive V-J spanning pairs. Both TCR α chains and β chains were enriched. TRBV18 usage is the highest in the P7 CD4+ population (18.1%), and TRBV5-1 usage is the highest in the P7 CD8+ population (12.1%). TRBV19 and TRBV20-1 segments are present in a high percentage of both P7 and P9 sequenced T cells. Remarkably, the alpha and beta chain combination of TRAV41-TRBV18 accounts for 13.5% of the CD4+ population of P7 patient. Compared to current Ni specific T cell repertoire studies of contact dermatitis, the Vα and Vβ usages of these joint implant failure patients were different. This could be due to the different availability of self-peptides in these two different tissues. However, TRBV19 (Vβ17) was among frequently used TCR β chains, which are common in previous reports. This implies that some pathogenic T cells could be similar in Ni2+ hypersensitivities in skin and joints. The alignment of the TCR CDR3β sequences showed a conserved glutamic acid (Glu) that could potentially interact with Ni2+. The study of these Ni2+ specific TCRs may shed light on the molecular mechanism of T cell activation by low molecular weight chemical haptens.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The T Cell Repertoires from Nickel Sensitized Joint Implant Failure Patients

Chen

Zhang

Pacheco

et al. 2021

IJMS

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“…Thus, activated NK cell might amplify the immune reaction via secretion of IFN‐γ, additionally activating dendritic cells, which leads to enhanced T‐cell responses. Furthermore, nickel‐specific CD4+ and CD8+ T cells have been described in nickel‐allergic patients being capable to produce IFN‐γ and granzyme B 40 . Earlier studies suggest that CD8+ T cells selectively kill human IFN‐γ‐primed keratinocytes, rendering them prone toward T H 1‐dependent cytotoxicity 41 .…”

Section: Discussionmentioning

confidence: 99%

Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis

Wisgrill

Werner

Jalonen

et al. 2020

Allergy

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Background Nickel‐induced allergic contact dermatitis (nACD) remains a major occupational skin disorder, significantly impacting the quality of life of suffering patients. Complex cellular compositional changes and associated immunological pathways are partly resolved in humans; thus, the impact of nACD on human skin needs to be further elucidated. Methods To decipher involved immunological players and pathways, human skin biopsies were taken at 0, 2, 48, and 96 hours after nickel patch test in six nickel‐allergic patients. Gene expression profiles were analyzed via microarray. Results Leukocyte deconvolution of nACD‐affected skin identified major leukocyte compositional changes at 48 and 96 hours, including natural killer (NK) cells, macrophage polarization, and T‐cell immunity. Gene set enrichment analysis mirrored cellular‐linked functional pathways enriched over time. NK cell infiltration and cytotoxic pathways were uniquely found in nACD‐affected skin compared to sodium lauryl sulfate–induced irritant skin reactions. Conclusion These results highlight key immunological leukocyte subsets as well as associated pathways in nACD, providing insights into pathophysiology with the potential to unravel novel therapeutic targets.

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“…So far, a comprehensive analysis of the Ni‐reactive TCR repertoire has been missing due to technological limitations. Only β‐chains were analyzed because many V segment antibodies are available and the limited number of J segments facilitates multiplex PCR approaches 22,25,26 …”

Section: Introductionmentioning

confidence: 99%

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

Aparicio‐Soto

Riedel

Leddermann

et al. 2020

Allergy

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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 NiSO 4 ., TCR α-and β-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. Results: Stimulation of PBMCs with NiSO 4 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 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Identification and Characterization of Circulating Naïve CD4+ and CD8+ T Cells Recognizing Nickel

Cited by 14 publications

References 54 publications

The T Cell Repertoires from Nickel Sensitized Joint Implant Failure Patients

The T Cell Repertoires from Nickel Sensitized Joint Implant Failure Patients

Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis

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

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