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 rtp to 96 hours. A small bur 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 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 nor 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.