title: Ex vivo expanded regulatory T cells CD4+CD25+FoxP3+CD127Lowdevelop strong immunosuppressive activity in patients with remitting-relapsing multiple sclerosis.
abstract: Multiple sclerosis (MS) is an autoimmune disease characterized by defect in regulatory function of CD4+CD25+T cells. We demonstrated difference in proportion of regulatory T cells CD4+CD25+FoxP3+CD127low(Tregs) within the same patients' relapse and remission. Proportion of peripheral Tregs (pTregs) dropped almost two times in the relapse compare to remission. Levels of pTregs in patients' remission were lower than in healthy donors. Suppressive ability of pTregs was decreased in MS patients compared to healthy donors. Injections of expanded ex vivo autologous Tregs (eTregs) could be helpful in bringing up the level of Tregs in patients' blood. We developed a simple method for ex vivo expansion of autologous Tregs within a short period of time. The final pool of cells consisted of 90-95% eTregs. When we started the culture with 10-20 × 106CD4+T cells, we yield 300-400 × 106eTregs in a week. Expression of FoxP3 and Helios was calculated by two methods. Expanded ex vivo patients' and donors' Tregs were characterized by increased from three to five times expression of FoxP3, as well as almost doubled Helios expression. Peripheral Tregs in MS patients have decreased demethylation of FoxP3 gene promoter in comparison with donors. On the contrary, eTregs showed stable up-regulated demethylation without difference between MS patients and donors. MS patients' and donors' eTregs have much more suppressive ability than pTregs. Our data showed that eTregs can be applied as immunotherapy for MS patients and other autoimmune diseases if further investigated.
authors.affiliation: a Pirogov Russian National Research Medical University , Moscow , Russia.
authors.forename: Gelena V
authors.initials: GV
authors.lastname: Lifshitz
authors.affiliation: a Pirogov Russian National Research Medical University , Moscow , Russia.|b Regenex LLC, Skolkovo Innovation Center , Moscow , Russia , and.
authors.forename: Dmitry D
authors.initials: DD
authors.lastname: Zhdanov
authors.affiliation: a Pirogov Russian National Research Medical University , Moscow , Russia.|b Regenex LLC, Skolkovo Innovation Center , Moscow , Russia , and.
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Lokhonina
authors.affiliation: b Regenex LLC, Skolkovo Innovation Center , Moscow , Russia , and.|c Neurology Scientific Research Institute , Moscow , Russia.
authors.forename: Daria D
authors.initials: DD
authors.lastname: Eliseeva
authors.affiliation: a Pirogov Russian National Research Medical University , Moscow , Russia.|b Regenex LLC, Skolkovo Innovation Center , Moscow , Russia , and.
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Lyssuck
authors.affiliation: c Neurology Scientific Research Institute , Moscow , Russia.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Zavalishin
authors.affiliation: a Pirogov Russian National Research Medical University , Moscow , Russia.|b Regenex LLC, Skolkovo Innovation Center , Moscow , Russia , and.
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Bykovskaia
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Autoimmune disease; Helios; T cell specific demethylation region; Tregs expansion; demethylation level