Identification and frequency of circulating CD 4 + T lymphocytes specific to B enzylpenicillin in healthy donors

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 CD 4 + 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 CD 4 + T lymphocytes in healthy donors. Methods Co‐cultures were established with CD 4 + T lymphocytes from healthy donors and mature autologous dendritic cells loaded with benzylpenicillin coupled to human serum albumin. CD 4 + T lymphocytes were stimulated once a week for 4 weeks with benzylpenicillin coupled to human serum albumin. The CD 4 + T ‐cell response was measured using an interferon‐γ ELISPOT assay. Frequency of benzylpenicillin‐specific naive CD 4 + T lymphocytes was then calculated using the P oisson distribution law. Results Results showed the presence of benzylpenicillin‐specific CD 4 + 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 CD 4 + T cells. Experiments performed on naive ( CD 45 RA + ) and on memory ( CD 45 RO + ) CD 4 + T lymphocytes showed that these benzylpenicillin‐specific CD 4 + T lymphocytes belonged to the naive T ‐cell subpopulation. Conclusion This study showed for the first time the existence of naive CD 4 + T lymphocytes specific to benzylpenicillin in healthy donors.