TH2 lymphocytes from atopic patients treated with immunotherapy undergo rapid apoptosis after culture with specific allergens

Background: In atopic patients treatment with specific immunotherapy (SIT) induced a shift in the balance of T-cell immune response away from a T(H)2-type (producing mostly IL-4) in favor of a T(H)1-type T-lymphocyte response (with the preferential production of IFN-gamma). However, the mechanisms through which SIT acts are less clear. We have recently shown that allergens may induce an activation-induced cell death process in lymphocytes from SIT-treated atopic patients. Objective: This study aimed to determine whether allergen-induced apoptosis ran occur in a specific subset of cells, Methods: The study was performed in lymphocytes from normal subjects and atopic patients, some of whom were treated with SIT, Cells were cultured in the presence of gramineous pollen (Lolium perenne) allergenic extracts. Cell phenotype and intracellular cytokine expression were measured by means of fluorescent mAbs. Apoptosis was measured by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling. Fluorescence was analyzed in a FAC-Scan flow cytometer, and the data were evaluated with Consort 30 software. R Results: Our results showed that allergens induce apoptosis of lymphocytes in SIT-treated atopic patients. Apoptosis occurs mainly in T(H)2 lymphocytes with the IL-4(+)/CD4(+) phenotype and subsequently increases the percentage of IFN-gamma (+) cells in the culture. Conclusion: These results suggest that the shift from T(H)2 to T(H)1 induced by SIT in atopic patients may be mediated, at least in part, by the induction of an activation-induced cell death process in allergen-responder T(H)2 cells.