Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells.
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 CD62L(hi) T cells), T cells displayed CD3(low)CD5(hi) phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62L(hi) T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3(low)CD5(hi) phenotype, followed by a CD3(low)CD5(low) phenotype. Spleens of old mice with the CD3(low)/CD5(hi) 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 TCRβ transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace.


CONCLUSIONS
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.
Center for Cancer and Immunology Research, Children's Research Institute, Washington, DC, USA.
Zohreh
Z
Tatari-Calderone
Milica
M
Stojakovic
Ramita
R
Dewan
Gama
G
Le Bouder
Dragana
D
Jankovic
Stanislav
S
Vukmanovic
D000375:Aging / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000601:surgery
D015415:Biomarkers; D017252:CD3 Complex; D018956:CD5 Antigens; D016753:Interleukin-10