Identification and characterization of a naïve <scp>CD</scp>8+ T cell repertoire for benzylpenicillin

Bechara, Rami; Maillère, Bernard; Joseph, Delphine; Weaver, Richard J.; Pallardy, Marc

doi:10.1111/cea.13338

Cited by 14 publications

(24 citation statements)

References 31 publications

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“…Previous works performed on nickel allergic patients showed a frequency of nearly 100 to 1,000-fold higher than our findings (34). However, the frequencies of naïve T cells recognizing benzylpenicillin (BP) (39, 45, 46) and immunogenic therapeutic antibodies (40) in non-immunized individuals were in the same range as those found in our study. It is important to note that the frequency of nickel-recognizing naïve T cells that we identified could still be an underestimation because of the use of nickel-loaded DCs, whereas it was shown that the activation of some nickel-specific T-cell lines (such as clone SE9) requires the persistent presence of nickel in the culture medium (20).…”

Section: Discussionsupporting

confidence: 79%

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

et al. 2019

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Allergic contact dermatitis caused by contact sensitizers is a T-cell-mediated inflammatory skin disease. The most prevalent contact allergens is nickel. Whereas, memory T cells from nickel-allergic patients are well-characterized, little is known concerning nickel-specific naïve T-cell repertoire. The purpose of this study was to identify and quantify naïve CD4+ and CD8+ T cells recognizing nickel in the general population. Using a T-cell priming in vitro assay based on autologous co-cultures between naïve T cells and dendritic cells loaded with nickel, we were able to detect a naïve CD4+ and CD8+ T-cell repertoire for nickel in 10/11 and 7/8 of the tested donors. We calculated a mean frequency of 0.49 nickel-specific naïve CD4+ T cells and 0.37 nickel-specific naïve CD8+ T cells per million of circulating naïve T cells. The activation of these specific T cells requires MHC molecules and alongside IFN-γ production, some nickel-specific T-cells were able to produce granzyme-B. Interestingly, nickel-specific naïve CD4+ and CD8+ T cells showed a low rate of cross-reactivity with cobalt, another metallic hapten, frequently mixed with nickel in many alloys. Moreover, naïve CD4+ T cells showed a polyclonal TCRβ composition and the presence of highly expanded clones with an enrichment and/or preferentially expansion of some TRBV genes that was donor and T-cell specific. Our results contribute to a better understanding of the mechanism of immunization to nickel and propose the T-cell priming assay as a useful tool to identify antigen-specific naïve T cells.

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Section: Discussionsupporting

confidence: 79%

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

et al. 2019

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“…A study has identified two target peptides of human serum albumin (HSA) for benzylpenicillin, to which this drug was covalently bound on lysines 159 and 525, which were able to induce specific proliferation of T cells from BL‐allergic patients . Another study has suggested that patients could be immunized by benzylpenicillin‐haptenated peptides from proteins generated in dendritic cells during the processing and presentation to T cells . Moreover, CLV binds to Lys 195 and 475 residues of HSA, forming adducts able to activate basophils in 69% of CLV‐allergic patients .…”

Section: New Understanding Of Dhr Mechanismmentioning

confidence: 99%

“…140 Another study has suggested that patients could be immunized by benzylpenicillin-haptenated peptides from proteins generated in dendritic cells during the processing and presentation to T cells. 141 Moreover, CLV binds to Lys 195 and 475 residues of HSA, forming adducts able to activate basophils in 69% of CLV-allergic patients. 120…”

Section: Ige-mediated Reactionsmentioning

confidence: 99%

Recent developments and highlights in drug hypersensitivity

Mayorga

Fernandez

Montañez

et al. 2019

Allergy

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Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management.Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication.Recent developments over the last 2 years and highlights about risk factors, diagnostic approaches, mechanisms involved as well as prevention actions, and management have been reviewed. In these papers, it has been outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, which will improve the management and treatment of patients with DHRs. K E Y W O R D Sallergy diagnosis, allergy treatment, basic mechanisms, drug allergy, epidemiology | 2369

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“…Previous studies with PBMCs from tolerant donors have reported a repertoire of naïve CD4 + and CD8 + T-cells that can be activated with benzylpenicillin. [15][16][17] This observation may be related to the fact that most of the general population in Europe has been exposed to BL antibiotics throughout their life. This exposure could also explain the detection of AX-specific T-cell clones in Clav-allergic patients and vice versa, that could be reinforced by the fact that both drugs are administered simultaneously in therapeutical treatments.…”

Section: Discussionmentioning

confidence: 99%

Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity

Ariza

Fernandez

Meng

et al. 2020

Allergy

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Background: Betalactam (BL) antibiotics are the most common cause of drug hypersensitivity. Amoxicillin (AX), which is often prescribed alongside clavulanic acid (Clav), is the most common elicitor. The aim of this study was to determine whether AX and Clav-responsive T-cells are detectable in patients with immediate hypersensitivity to AX-Clav, to assess whether these T-cells display the same specificity as that detected in skin and provocation testing, and to explore T-cell activation pathways. Methods: Drug-specific T-cell clones were generated from immediate hypersensitive patients´ blood by serial dilution and repetitive mitogen stimulation. Antigen specificity was assessed by measurement of proliferation and cytokine release. CD4 + /CD8 + phenotype and chemokine receptor expression were analyzed by flow cytometry. Results: 110 AX-specific and 96 Clav-specific T-cell clones were generated from seven patients with positive skin test to either AX or Clav. Proliferation of AX-and Clavspecific clones was dose-dependent, and no cross-reactivity was observed. AX-and Clav-specific clones required antigen-presenting cells to proliferate, and drugs were presented to CD4 + and CD8 + T-cells by MHC class-II and I, respectively. A higher secretion of IL-13 and IL-5 was detected in presence of the culprit drug compared with the alternative drug. Clones expressed CD69, CCR4, CXCR3, and CCR10. Conclusions: Our study details the antigen specificity and phenotype of T-cell clones generated from patients with AX-Clav-induced immediate hypersensitivity diagnosed by positive skin test. AX-and Clav-specific clones were generated from patients irrespective of whether AX or Clav was the culprit, although differences in cytokine secretion were observed. | 2563 ARIZA et Al.

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Identification and characterization of a naïve CD8+ T cell repertoire for benzylpenicillin

Cited by 14 publications

References 31 publications

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

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

Recent developments and highlights in drug hypersensitivity

Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity

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