Kinetics of cell infiltration and cytokine messenger RNA expression after intradermal challenge with allergen and tuberculin in the same atopic individuals

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 T_H2-like (interleukin-4 [IL]-4 and IL-5 mRNA⁺) cytokine profile, whereas in delayed-type hypersensitivity (DTH) there was a predominant T_H1-type pattern. Objective: The study was designed to examine the kinetics of accumulation of inflammatory cells and cells expressing mRNA for T_H2- or T_H1-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-γ 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-γ 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 T_H2-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 T_H1-type cytokines are not apparent until 24 to 48 hours. In LPR there is a T_H1-type (or possibly T_H0) component at 48 to 96 hours, and in DTH there is an additional T_H2 T_H0 response.