Characterizing the circulating, gliadin-specific CD4 memory T cells in patients with celiac disease: linkage between

Abstract: Celiac disease (CD) is a chronic, im-mune-mediated disorder of the gut, driven by T cells reacting locally to a distinct antigen, gliadin. Thus, CD offers the opportunity to study the T cell memory response to gliadin and whether gut tro-pism and T helper cell type 1 (Th1) polarization, which characterize the effector phase, are pre-served in the memory progeny. It is notable that previous studies yielded conflicting results as to the presence of gliadin-specific memory CD4 T cells in the peripheral blood of CD patients. However, we used a different and highly sensitive approach based on fluorescein-derived label dilution, whereby the memory cells are identified operation-ally by their greater capacity to proliferate upon re-encounter with antigen. Thus, using flow cytom-etry, we could resolve multiple successive genera-tions as well as immunophenotype the dividing cells. Here, we show that the peripheral blood lym-phocyte of some CD patients on a gliadin-free diet, but not healthy donors, contains a detectable pop-ulation of CD4 memory T cells specific for de-amidated gliadin. Moreover, these gliadin-specific memory T cells are marked by a distinctive pheno-type: They express high levels of the gut-homing 7 integrins and primarily produce interferon- and tumor necrosis factor . We conclude that memory for gliadin-derived antigens within the cir-culating CD4 T cells is linked with gut tropism as well as Th1 polarization. J. Leukoc. Biol. 79