Human Primary Adenotonsillar Naïve Phenotype CD45RA+ CD4+ T Lymphocytes Undergo Apoptosis Upon Stimulation With a High Concentration of CD3 Antibody

Abstract

Young children need to develop immune tolerance to harmless foreign antigens such as digested nutrients and various inhaled airborne antigens. Because of its anatomical location, pharyngeal adenotonsillar tissue is a potential site for the establishment of this immune tolerance. To characterize possible mechanisms of peripheral immune tolerance, we studied human primary adenotonsillar naïve phenotype CD45RA(+) CD4(+) T cells, which represent cells that have not previously encountered foreign antigens. It was found that these CD45RA(+) CD4(+) T cells expressed higher levels of the activation marker CD69 as compared with peripheral blood CD45RA(+) CD4(+) T cells. Upon stimulation with a high concentration of CD3 antibody, which mimics the encounter of a high antigen dose, adenotonsillar CD45RA(+) CD4(+) T lymphocytes, but not peripheral blood CD45RA(+) CD4(+) T cells, underwent apoptosis. After 6 h stimulation with a high concentration of CD3 antibody, over 25% of the cells were apoptotic. Interfering with the Fas-FasL interaction with recombinant Fas or an antibody against Fas-ligand partially inhibited apoptosis. Our study results suggest that high concentrations of antigens, such as various nutrients and airborne antigens, may induce peripheral immune tolerance by selectively deleting naïve phenotype CD45RA(+) CD4(+) T cells via T-cell receptor-triggered apoptosis in human adenotonsillar tissue.