Neonatal thymectomy prolongs the permeability of enteric antigens and promotes the strong activation of peripheral CD4 T cells (P3258)

Abstract

Abstract Thymectomy (Tx) during the neonatal period (days 2 to 4) leads to the development of a spectrum of organ-specific autoimmune diseases in several strains of adult mice. The etiology of this intriguing phenomenon is yet to be fully elucidated, although it is widely believed to be a consequence of two controversial mechanisms: (1) production of pathogenic CD4+ T cells from neonatal-specific defect in central tolerance, and (2) abolition in the production of regulatory T cells (Tregs), which are believed to develop later in ontogeny than typical T cells. We hereby suggest an additional mechanism that may contribute to the onset of autoimmunity, perhaps by instigating the chronic activation of autoreactive T cells. We found that neonatal C57BL/6 mice display a defect in their ability to induce efficient tolerance to enteric antigens during the first several days of their life, and neonatal thymectomy significantly prolongs the period of this defect. Hence, while enteric antigens induce strong activation of peripheral CD4+ T cells only during the first several days in euthymic neonatal mice, such responses continue for several weeks in d3 thymectomized mice. The unregulated responses to enteric antigens in return may lead to inadvertent activation of autoreactive T cells.