title: Kinetics of cell infiltration and cytokine messenger RNA expression after intradermal challenge with allergen and tuberculin in the same atopic individuals.
abstract: BACKGROUND
  Previous studies, in which one time point was used, have shown that cells infiltrating skin biopsy specimens taken during allergen-induced late-phase responses (LPR) had a TH2-like (interleukin-4 [IL]-4 and IL-5 mRNA+) cytokine profile, whereas in delayed-type hypersensitivity (DTH) there was a predominant TH1-type pattern.
  
  
  OBJECTIVE
  The study was designed to examine the kinetics of accumulation of inflammatory cells and cells expressing mRNA for TH2- or TH1-type cytokines in LPR and DTH elicited simultaneously in the same subjects.
  
  
  METHODS
  Immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase technique) and in situ hybridization were used to analyze skin biopsy specimens taken during allergen-induced LPR.
  
  
  RESULTS
  In LPR elevated numbers of CD3+ and CD4+ cells, eosinophils, neutrophils, and IL-4 and IL-5 mRNA+ cells were detected as early as 1 hour after allergen challenge, with a peak at 6 hours, which was maintained for up to 96 hours. A small but significant delayed increase in macrophages, CD8+ and CD25+ cells, and IL-2 and interferon-gamma mRNA+ cells was also observed, but only at the 48-hour and 96-hour time points. In contrast, in DTH the numbers of CD3+, CD4+, and mRNA+ cells for IL-2 and interferon-gamma were not elevated until 24 hours after challenge and peaked at 48 hours after injection. At 48 hours there was an additional small but significant increase in IL-4 and IL-5 mRNA+ cells. For both LPR and DTH the kinetics of the increases in inflammatory cells and cytokine mRNA-expressing cells paralleled the clinical response.
  
  
  CONCLUSIONS
  In LPR accumulation of T cells and granulocytes, together with cells expressing mRNA encoding for TH2-type cytokines, is relatively rapid (i.e., within 1 to 6 hours), whereas in DTH the T cell/macrophage infiltration and appearance of cells expressing TH1-type cytokines are not apparent until 24 to 48 hours. In LPR there is a TH1-type (or possibly TH0) component at 48 to 96 hours, and in DTH there is an additional TH2/TH0 response.
authors.affiliation: Department of Allergy and Clinical Immunology, Royal Brompton National Heart and Lung Institute, London, England.
authors.forename: A
authors.initials: A
authors.lastname: Tsicopoulos
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
authors.forename: A
authors.initials: A
authors.lastname: Haczku
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobson
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: J
authors.initials: J
authors.lastname: North
authors.forename: J
authors.initials: J
authors.lastname: Barkans
authors.forename: C J
authors.initials: CJ
authors.lastname: Corrigan
authors.forename: Q
authors.initials: Q
authors.lastname: Meng
authors.forename: R
authors.initials: R
authors.lastname: Moqbel
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D002465:Cell Movement; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007271:Injections, Intradermal; D007700:Kinetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D011930:Reaction Time; D014373:Tuberculin / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D012333:RNA, Messenger; D014373:Tuberculin