PMID- 33504740 OWN - NLM STAT- MEDLINE DCOM- 20211109 LR - 20211109 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 44 IP - 4 DP - 2021 Apr 1 TI - Characterization of an Expanded IL-10-Producing-Suppressive T Cell Population Associated with Immune Tolerance. PG - 585-589 LID - 10.1248/bpb.b19-01072 [doi] AB - 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 (GPI(325-339))-induced arthritis were treated with FTY720 (1 mg/kg, per os) and GPI(325-339) (10 microg/mouse, intravenously) 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 immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif 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 T helper 1 (Th1) response, produced high levels of both interleukin (IL)-10 and interferon (IFN)-gamma. 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. FAU - Yoshida, Yuya AU - Yoshida Y AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. FAU - Mikami, Norihisa AU - Mikami N AD - Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University. FAU - Nakanishi, Yusuke AU - Nakanishi Y AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. FAU - Saimoto, Maya AU - Saimoto M AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. FAU - Nagaike, Arata AU - Nagaike A AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. FAU - Shimono, Haruka AU - Shimono H AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. FAU - Nakano, Shohei AU - Nakano S AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. FAU - Tsuji, Takumi AU - Tsuji T AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. FAU - Kohno, Takeyuki AU - Kohno T AD - Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University. LA - eng PT - Journal Article DEP - 20210126 PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Antigens, CD) RN - 0 (Cytokines) RN - 0 (Glucocorticoid-Induced TNFR-Related Protein) RN - 0 (Receptors, Immunologic) RN - 0 (T cell Ig and ITIM domain protein, mouse) RN - 0 (Tnfrsf18 protein, mouse) RN - 130068-27-8 (Interleukin-10) RN - EC 3.6.1.5 (Apyrase) RN - EC 3.6.1.5 (CD39 antigen) RN - EC 5.3.1.9 (Glucose-6-Phosphate Isomerase) RN - G926EC510T (Fingolimod Hydrochloride) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Apyrase/metabolism MH - Arthritis/chemically induced MH - CD4-Positive T-Lymphocytes/metabolism MH - Cytokines/metabolism MH - Fingolimod Hydrochloride/pharmacology MH - Flow Cytometry MH - Glucocorticoid-Induced TNFR-Related Protein/metabolism MH - Glucose-6-Phosphate Isomerase/pharmacology MH - Immune Tolerance/*immunology MH - Interleukin-10/*metabolism MH - Mice MH - Mice, Inbred DBA MH - Models, Animal MH - Receptors, Immunologic/metabolism MH - T-Lymphocyte Subsets/*immunology/*metabolism MH - T-Lymphocytes, Regulatory/immunology OTO - NOTNLM OT - T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain OT - fingolimod OT - glucocorticoid-induced tumor necrosis factor receptor-family related gene/protein OT - immune tolerance OT - interleukin-10 OT - pathogenic antigen EDAT- 2021/01/29 06:00 MHDA- 2021/11/10 06:00 CRDT- 2021/01/28 05:34 PHST- 2021/01/29 06:00 [pubmed] PHST- 2021/11/10 06:00 [medline] PHST- 2021/01/28 05:34 [entrez] AID - 10.1248/bpb.b19-01072 [doi] PST - ppublish SO - Biol Pharm Bull. 2021 Apr 1;44(4):585-589. doi: 10.1248/bpb.b19-01072. Epub 2021 Jan 26.