INFLUENCE OF GRASS POLLEN IMMUNOTHERAPY ON CELLULAR INFILTRATION AND CYTOKINE EXPRESSION DURING ALLERGEN-INDUCED LATE-PHASE CUTANEOUS RESPONSES

Abstract

Purpose of the Study. The mechanism by which immunotherapy (IT) provides its beneficial effects are poorly understood. This study examines the effects of grass pollen IT on cellular infiltration and cytokine mRNA expression during allergen induced late phase cutaneous responses. Methods. Forty subjects were enrolled in this double blind, placebo controlled study to receive twice weekly injections of either a standardized grass pollen extract or placebo. Once maintenance was reached, injections were administered monthly for 9 months. Skin biopsies following intradermal infection with Timothy extract were performed prior to and following IT. Monoclonal antibody staining was used to detect surface markers on lymphocytes. In situ hybridization was used to identify cells expressing cytokine mRNA. Findings. Both patient groups were matched for age, disease severity, and duration. Thirty-seven patients (17 placebo, 20 active) completed the study. The treated group had a significant decrease in symptoms, medication use, and size of the immediate and late phase reaction (LPR) after intradermal allergen injection upon completion of the IT. Skin biopsy cell counts from actively treated subjects obtained after subcutaneous allergen challenge showed a significant decrease in T helper and eosinophil cell numbers compared to the placebo group. Increases in the expression of CD25 and HLA-DR (markers of T cell activation) were seen in the treatment group. No differences in amount of HA and IL5 mRNA-expressing cells (TH2) were noted, but there was an increase in IFN-γ and IL2 mRNA expressing cells (ie, TH1) in the actively treated group. A significant correlation was noted between the size of the LPR and the numbers of CD4+ cells in the placebo group.