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Identification and frequency of circulating CD4+ T lymphocytes specific to Benzylpenicillin in healthy donors

Authors


  • Edited by: Pascal Demoly

Correspondence

Marc Pallardy, PhD, Université Paris-Sud, INSERM UMR-S 996, UFR Pharmacie, 5 Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.

Tel.: +00-33-(0)1-46-83-54-92

Fax: +00-33-(0)1-46-83-54-96

E-mail: marc.pallardy@u-psud.fr

Abstract

Background

Drug hypersensitivity is known to rely on a drug-specific T-cell response. Amplitude of antigen-specific T-cell response is partly controlled by the size of the antigen-specific naïve CD4+ T-cell repertoire, but estimate of this repertoire has never been investigated for allergenic drugs. The purpose of this study was to evaluate the frequency of benzylpenicillin-specific CD4+ T lymphocytes in healthy donors.

Methods

Co-cultures were established with CD4+ T lymphocytes from healthy donors and mature autologous dendritic cells loaded with benzylpenicillin coupled to human serum albumin. CD4+ T lymphocytes were stimulated once a week for 4 weeks with benzylpenicillin coupled to human serum albumin. The CD4+ T-cell response was measured using an interferon-γ ELISPOT assay. Frequency of benzylpenicillin-specific naive CD4+ T lymphocytes was then calculated using the Poisson distribution law.

Results

Results showed the presence of benzylpenicillin-specific CD4+ T lymphocytes in 9 of 10 tested healthy donors irrespective of their HLA typing, with a mean frequency of 0.29 cells per million of CD4+ T cells. Experiments performed on naive (CD45RA+) and on memory (CD45RO+) CD4+ T lymphocytes showed that these benzylpenicillin-specific CD4+ T lymphocytes belonged to the naive T-cell subpopulation.

Conclusion

This study showed for the first time the existence of naive CD4+ T lymphocytes specific to benzylpenicillin in healthy donors.

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