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OP0010 Autologous Hematopoietic Stem Cell Transplantation Increases T-Cell PD-1 Expression and Regulatory Mechanisms in Systemic Sclerosis Patients
  1. L.C.M. Arruda1,2,
  2. M.C. Oliveira3,
  3. D.A. Moraes3,
  4. D.T. Covas1,
  5. K.C.R. Malmegrim1
  1. 1National Institute of Science and Technology in Stem Cells and Cell Therapy, Regional Hemotherapy Center of the Ribeirão Preto Medical School
  2. 2Biochemistry and Immunology, University of São Paulo
  3. 3Division of Clinical Immunology, Internal Medicine Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

Abstract

Background Autologous Hematopoietic Stem Cell Transplantation (AHSCT) has been proved as an alternative for the treatment of severe and progressive systemic sclerosis (SSc) patients [1]. To understand the therapeutic mechanisms enrolled in AHSCT and to further improve its efficacy, we aimed to evaluate the post-transplantation immune reconstitution [2]

Objectives To evaluate the immune reconstitution after AHSCT through quantification of total, naive and memory CD4+ T-cells, regulatory T-cells and of exhausted T- and B-cells.

Methods Peripheral blood was collected from nine diffuse SSc patients before and at 6, 12, 18 and 24 months post-AHSCT. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry.

Results Total CD3+CD4+ T-cell counts were significantly decreased (P<0.01) from 6-24 months post-AHSCT when compared to baseline due intense depletion of CD4+CD45RO-CD27+ naive and CD4+CD45RO+CD27+ central-memory cells. No changes were detected in the CD4+CD45RO-CD27- effector or in the CD4+CD45RO+CD27- effector memory T-cell numbers (P>0.05). At the same time, higher counts of CD4+CD25hiFoxP3+ regulatory T-cells (Tregs) were observed at 12 months post-AHSCT when compared to baseline (P<0.05), indicating an increasing proportion of Treg/CD3+CD4+ T-cell ratio from 6 months until the end of follow-up (P<0.01). Higher expression (%) of CTLA-4 on CD4+CD25hi T-cells was observed only at 24 months post-AHSCT (P<0.05), and increasing GITR expression (%) was observed from 6-24 months (P<0.05). PD-1 expression (%) increased at 6 and 12 months post-AHSCT in CD3+CD4+ (P<0.01) and in CD3+CD8+ T-cells (P<0.05) when compared to baseline. No changes were observed in CD19+ B-cells.

Conclusions Our results suggest improvement of peripheral immunoregulatory mechanisms and depletion of central memory CD4+ T-cells after AHSCT, which may contribute to reestablishment of self-tolerance and to control of autoimmunity in SSc patients.

References

  1. van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014 Jun; 311(24):2490-2498.

  2. Baraut J, Grigore EI, Jean-Louis F, Khelifa SH, Durand C, Verrecchia F, et al. Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study. Bone Marrow Transplant. 2014 Mar; 49(3):349-354.

Acknowledgements Funding was provided by CNPq and by the Sao Paulo Research Foundation (FAPESP).

Disclosure of Interest None declared

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