Increased Foxp3(+) Treg cell activity reduces dendritic cell co-stimulatory molecule expression in aged mice.
As potent suppressors of immune responses to self- and foreign-antigens, Foxp3(+) Treg cells are suspected to be involved in immunosuppression leading to cancer, neurodegeneration and infection. Since ageing is associated with increased incidence of these diseases, we compared Treg activity in blood, lymphoid organs and lungs of young (5-6 months) and old (21-22 months) mice. Both the proportion and absolute number of Foxp3(+) CD4(+) Treg cells increased with age in secondary lymphoid organs but not in blood and lungs as compared to Foxp3(-) CD4(+) T cells. Although numbers of thymic and naïve conventional T and Treg cells decreased with age, Treg cells with memory/effector phenotype increased disproportionately in peripheral lymphoid tissues. In addition, CD40 and CD86 co-stimulatory molecule expression by lymph node dendritic cells was impaired in old mice and could be restored to levels of young mice by inactivating Treg cells with anti-CD25 monoclonal antibodies. These findings have important implications for the understanding of age-related immune dysfunction.
Chiu
Bo-Chin
BC
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Stolberg
Valerie R
VR
Zhang
Haoming
H
Chensue
Stephen W
SW
D000367:Age Factors; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007108:Immune Tolerance; D007156:Immunologic Memory; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology
D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000242:Cyclic AMP