Elucidation of cellular and molecular events involved in the effect immunomodulator of IgG antibodies on the thymic differentiation of TCD4 lymphocytes and TCD8 focusing on atopic diseases

Abstract

Although used for therapeutic purposes in several pathological processes, the precise mechanisms by which IgG antibodies can modulate immunity in the absence of antigen are not known. In recent years, several studies have shown that IgG antibodies can differentially play an immunomodulatory role on peripheral human T lymphocytes or on primary lymphoid organs such as the thymus. This effect seems to be dependent on the natural repertoire of IgG idiotypes produced by different groups of individuals in which the atopic state is determinant but has not yet been experimentally elucidated. Atopic Dermatitis (AD) is a chronic inflammatory dermatological disease whose development has not yet been fully clarified. However, it is known that the pathophysiology of AD is mediated by the activation of T±² lymphocytes (TCD4 and TCD8) with different patterns regarding the production of cytokines, which play a local (in the lesion) or systemic role. Additionally, the participation of T³´ lymphocytes in AD has been discussed, but has not yet been characterized.Recently, our group demonstrated that the repertoire of IgG antibodies naturally produced by patients who develop AD can modulate the production of cytokines by thymic T lymphocytes, inducing a profile similar to that observed in patients with AD, but in these studies, no approach to mechanisms was performed. Therefore, in this project we aim to experimentally elucidate some of the cellular and molecular mechanisms that mediate the effect of IgG antibodies from patients with AD on the thymic maturation of T±² lymphocytes (TCD4 and TCD8) and Tgd, in order to collaborate with the understanding of the pathophysiology of AD as well as human intrathymic regulatory mechanisms. (AU)