Characterization of an expanded IL-10-producing-suppressive T cell population associated with immune tolerance.

Abstract:

:An increase in the number of glucocorticoid-induced tumor necrosis factor receptor-family related gene/protein (GITR)+CD25- (or fork-head box protein 3: Foxp3-) CD4+ T cells, after treating a mouse model of arthritis with fingolimod (FTY720), and a pathogenic antigen may play a key role in the establishment of immune tolerance. In this study, we characterized a specific expanded T cell subset in this population.Mice with glucose-6-phosphate isomerase peptide (GPI325-339)-induced arthritis were treated with FTY720 (1 mg/kg, p.o.) and GPI325-339 (10 µg/mouse, i.v.) for five days, starting from the onset of symptoms. The expanded GITR+CD25- (or Foxp3-) CD4+ T cell population and its cytokine production were examined using flow cytometry. Furthermore, time-dependent changes in T-bet and/or early growth response gene 2 (Egr-2) expression in this T cell subset were examined.The density of T cell immunoreceptors with Ig and ITIM domains (TIGIT)+CD39+ cell subset in the GITR+Foxp3-CD4+ T cell population was significantly increased only in the combined treatment group, compared to that in the untreated and single-treatment groups. In the TIGIT+CD39+GITR+Foxp3-CD4+ T cell population, T-bet+Egr-2+/T-bet+Egr-2- cell ratio increased in the latter stage of the treatment. Furthermore, this T cell subset, which corresponded to a Th1 response, produced high levels of both interleukin (IL)-10 and interferon (IFN)-γ.In conclusion, expanded TIGIT+CD39+GITR+Foxp3-CD4+ T cells shifted from an effector Th1 to IL-10-producing-suppressor T cell phenotype, which may promote an immune-tolerant state.

journal_name

Biol Pharm Bull

authors

Yoshida Y,Mikami N,Nakanishi Y,Saimoto M,Nagaike A,Shimono H,Nakano S,Tsuji T,Kohno T

doi

10.1248/bpb.b19-01072

subject

Has Abstract

pub_date

2021-01-26 00:00:00

eissn

0918-6158

issn

1347-5215

pub_type

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