CD8+CD45RA+CCR7+FOXP3+ T Cells with Immunosuppressive Properties: A Novel Subset of Inducible Human Regulatory T Cells
Year: 2012
Type: article
Abstract: CD8 T cells stimulated with a suboptimal dose of anti-CD3 Abs (100 pg/ml) in the presence of IL-15 retain a naive phenotype with expression of CD45RA, CD28, CD27, and CCR7 but acquire new functions and differentiate into immunosuppressive T cells. CD8+CCR7+ regulatory T cells (Tregs) express FOXP3 and prevent CD4 T cells from responding to TCR stimulation and entering the cell cycle. Naive CD4 T cells are more susceptible to inhibition than memory cells. The suppressive activity of CD8+CCR7+ Tregs is not mediated by IL-10, TGF-β, CTLA-4, CCL4, or adenosine and relies on interference with very early steps of the TCR signaling cascade. Specifically, CD8+CCR7+ Tregs prevent TCR-induced phosphorylation of ZAP70 and dampen the rise of intracellular calcium in CD4 T cells. The inducibility of CD8+CCR7+ Tregs is correlated with the age of the individual with PBLs of donors older than 60 y yielding low numbers of FOXP3(low) CD8 Tregs. Loss of CD8+CCR7+ Tregs in the elderly host may be of relevance in the aging immune system as immunosenescence is associated with a state of chronic smoldering inflammation.
Source: The Journal of Immunology
Institutions: Stanford Medicine, Stanford University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: CD8 T Cells in Rheumatoid Arthritis, G1633945206, G273488510, G3926431530, G4155112483, Oligoclonal T Cell Expansion and Rheumatoid Arthritis, G442201000, G53705813, G6170789353, G64106078, Ocular Disease in Giant Cell Arteritis, Interactions Between Inflammation, Oxidant Stress and Cardiovascular Disease, Vaccination and infection: indicators of immunological health and responsiveness, G890287097, Vaccine and Infection Induced Immunity in the Young and Aged
OpenAlex ID: W2104829989