title: Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study.
abstract: The present pilot study aims to evaluate the frequency and the function of regulatory T (Treg) cells in patients with diffuse cutaneous SSc (dcSSc) before and after autologous hematopoietic SCT (aHSCT). Peripheral blood lymphocytes from seven dcSSc patients were analyzed before and 24 months after aHSCT and were compared with those from seven healthy donors (controls). Immunophenotyping of CD4(+)CD25(high)FoxP3(+) natural Treg (nTreg), CD4(+)CD25(+)TGF-β(+) and CD4(+)CD25(+)IL-10(+) adaptive Treg (aTreg) cell subsets was performed using four-color flow cytometry. Treg-suppressive capability was measured after coculture with autologous T effector cells by evaluation of T-cell proliferation using (3)H-thymidine incorporation. Peripheral CD4(+)CD25(high)FoxP3(+) (2±0.5 vs 4.2±1.1, P<0.01), CD4(+)CD25(+)TGF-β(+) (6.9±1.8 vs 14.6±5.0, P<0.05) and CD4(+)CD25(+)IL-10(+) (10.7±0.5 vs 16.1±3.2, P<0.01) Tregs as well as CD4(+)CD25(high)CD127(low) Tregs suppressive capacity (P<0.05) were decreased in dcSSc patients vs controls. After aHSCT (n=7), the percentages of CD4(+)CD25(high)FoxP3(+) (4.1±1.8) and CD4(+)CD25(+)IL-10(+) (15.7±2.2) Treg cells and the suppressive activity of CD4(+)CD25(high)CD127(low) were restored to the levels in controls. The decreased frequency and the functional defect of peripheral Treg cells from patients with dcSSc are reversed following aHSCT to reach those observed in controls. This pilot study brings evidence of an effective restoration of nTreg and aTreg subsets, and recovery of nTreg suppressive function following aHSCT.
authors.affiliation: INSERM U976 and Université Paris Diderot Sorbonne Paris Cité, Hôpital Saint-Louis, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Baraut
authors.affiliation: INSERM U976 and Université Paris Diderot Sorbonne Paris Cité, Hôpital Saint-Louis, Paris, France.
authors.forename: E I
authors.initials: EI
authors.lastname: Grigore
authors.affiliation: INSERM U976 and Université Paris Diderot Sorbonne Paris Cité, Hôpital Saint-Louis, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Jean-Louis
authors.affiliation: Service de Médecine Interne, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France.
authors.forename: S H
authors.initials: SH
authors.lastname: Khelifa
authors.affiliation: Service de Médecine Interne, Hôpital Hôtel Dieu, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Durand
authors.affiliation: INSERM U957 and Université Nantes Atlantique, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Verrecchia
authors.affiliation: 1] INSERM U976 and Université Paris Diderot Sorbonne Paris Cité, Hôpital Saint-Louis, Paris, France [2] Service de Médecine Interne, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Farge
authors.affiliation: INSERM U976 and Université Paris Diderot Sorbonne Paris Cité, Hôpital Saint-Louis, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Michel
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D045743:Scleroderma, Diffuse / Q000097:blood* / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014182:Transplantation, Autologous
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10