Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure.
Toxicol Appl Pharmacol
; 331: 69-75, 2017 09 15.
Article
em En
| MEDLINE
| ID: mdl-28554661
ABSTRACT
T cell mediated hypersensitivity to nickel (Ni2+) is one of the most common causes of allergic contact dermatitis. Ni2+ sensitization may also contribute to the failure of Ni2+ containing joint implants, and revision to non-Ni2+ containing hardware can be costly and debilitating. Previously, we identified Ni2+ mimotope peptides, which are reactive to a CD4+ T cell clone, ANi2.3 (Vα1, Vß17), isolated from a Ni2+ hypersensitive patient with contact dermatitis. This T cell is restricted to the major histocompatibility complex class II (MHCII) molecule, Human Leukocyte Antigen (HLA)-DR52c (DRA, DRB3*0301). However, it is not known if Ni2+ induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni2+ induced contact dermatitis. Here, we generated DR52c/Ni2+ mimotope tetramers, and used them to test if the same Ni2+ T cell activation mechanism could be generalized to Ni2+ sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3T cell transfectomas. The DR52c/Ni2+ mimotope tetramer detected Ni2+ reactive CD4+ T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni2+ sensitized by patch testing and a positive Ni2+ LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni2+ stimulation induced the expansion of Vß17 positive CD4+ T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vß17 usage in Ni2+ sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni2+ independent mimotope tetramers may be a useful tool to identify the Ni2+ reactive CD4+ T cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Falha de Prótese
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Linfócitos T CD4-Positivos
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Artroplastia de Substituição
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Hipersensibilidade
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Níquel
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article