age-related accumulation of t cells with markers of relatively stronger autoreactivity leads to functional erosion of t cells与年龄相关的积累与标记t细胞相对更强的autoreactivity导致t细胞功能的侵蚀.pdfVIP

Tatari-Calderone et al. BMC Immunology 2012, 13:8 /1471-2172/13/8 RESEARCH ARTICLE Open Access Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells 1 1,2 1 1 3 Zohreh Tatari-Calderone , Milica Stojakovic , Ramita Dewan , Gama Le Bouder , Dragana Jankovic and Stanislav Vukmanovic1,2,4* Abstract Background: Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/ expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases. Results: The phenotype of T cells from aged mice (18-24 months) indicating functional TCR avidity (CD3 and CD5 expression) correlates with the level of preserved thymic function. In mice with moderate thymic output ( 30% of peripheral CD62Lhi T cells), T cells displayed CD3lowCD5hi phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62Lhi T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3lowCD5hi phenotype, followed by a CD3lowCD5low phenotype. Spleens of old mice with the CD3low/CD5hi T cell phenotype displayed increased levels of IL-10 mRNA, and their T cells could be induced to secrete IL-10 in vitro