title: Identification and frequency of circulating CD4(+) T lymphocytes specific to Benzylpenicillin in healthy donors.
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.
  
  
  CONCLUSIONS
  This study showed for the first time the existence of naive CD4(+) T lymphocytes specific to benzylpenicillin in healthy donors.
authors.affiliation: Université Paris-Sud, INSERM UMR 996, UFR Pharmacie, Châtenay-Malabry, France.
authors.forename: C
authors.initials: C
authors.lastname: Nhim
authors.forename: S
authors.initials: S
authors.lastname: Delluc
authors.forename: F
authors.initials: F
authors.lastname: Halgand
authors.forename: L
authors.initials: L
authors.lastname: de Chaisemartin
authors.forename: R J
authors.initials: RJ
authors.lastname: Weaver
authors.forename: N
authors.initials: N
authors.lastname: Claude
authors.forename: D
authors.initials: D
authors.lastname: Joseph
authors.forename: B
authors.initials: B
authors.lastname: Maillère
authors.forename: M
authors.initials: M
authors.lastname: Pallardy
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004342:Drug Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D058501:Enzyme-Linked Immunospot Assay; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D010400:Penicillin G / Q000276:immunology / Q000494:pharmacology*; D012016:Reference Values; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D010400:Penicillin G
keywords: T lymphocytes; benzylpenicillin; drug allergy