%0 Journal Article
%T Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells
%A Zohreh Tatari-Calderone
%A Milica Stojakovic
%A Ramita Dewan
%A Gama Le Bouder
%A Dragana Jankovic
%A Stanislav Vukmanovic
%J BMC Immunology
%D 2012
%I BioMed Central
%R 10.1186/1471-2172-13-8
%X 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. In contrast, downmodulation of CD5 was accompanied with reduced IL-10 expression and impaired anti-CD3 induced proliferation. Irrespective of the CD3/CD5 phenotype, reduced severity of experimental allergic myelitis occurred in old mice. In MTB TCR¦Â transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace.These findings suggest that age-associated dysfunctions of the immune system could in part be due to functional erosion of T cells devised to protect the hosts from the prolonged exposure to T cells with high-avidity for self.Immune system of elderly displays complex set of changes relative to young individuals. Of the many variations observed, altered T cell function is the most consistent and most dramatic one [1]. Despite relatively normal numbers of CD4+ and CD8+ lymphocytes, T-cell dependent functions of the immune system of aged individuals are defective, as evidenced by reduced DTH reactions and antibody production in response to vaccination and infection [2]. This could be due to reduced proliferation of T cells, evident at biochemical level by defects in proximal TCR signaling cascade activation [3-5] and calcium signaling [6], and at cellular level by defects in cytokine production
%U http://www.biomedcentral.com/1471-2172/13/8