Interleukin-10-mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen

Andrew Michael Hall, Frank James Ward, Mark Adrian Vickers, Lisa-Marie Stott, Stanislaw Urbaniak, Robert Norman Barker

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Regulatory T cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-gamma or to secrete the regulatory cytokine interleukin 10 when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4(+) phenotype. Serial results from individual patients demonstrated that this bias toward proliferative or interleukin-10 responses was unstable over time and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin 10 and dependent on cytotonic T lymphocyte-associated antigen (CTLA-4) costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease.
Original languageEnglish
Pages (from-to)4529-4536
Number of pages8
JournalBlood
Volume100
Issue number13
DOIs
Publication statusPublished - 15 Dec 2002

Fingerprint

T-cells
Autoantigens
Regulatory T-Lymphocytes
Interleukin-10
Epitopes
Blood
Erythrocytes
Cells
Autoimmune Hemolytic Anemia
Peptides
CTLA-4 Antigen
Cytokines
Peptide T
Epitope Mapping
T-Lymphocytes
Immune System Diseases
Cell proliferation
Pathology
Interferon-gamma
Blood Cells

Keywords

  • Adult
  • Aged
  • Anemia, Hemolytic, Autoimmune
  • Antigens, CD
  • Antigens, Differentiation
  • Autoantigens
  • Cells, Cultured
  • Epitopes
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance
  • Immunoconjugates
  • Immunophenotyping
  • Interferon-gamma
  • Interleukin-10
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Peptide Mapping
  • Rh-Hr Blood-Group System
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Helper-Inducer

Cite this

Interleukin-10-mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen. / Hall, Andrew Michael; Ward, Frank James; Vickers, Mark Adrian; Stott, Lisa-Marie; Urbaniak, Stanislaw; Barker, Robert Norman.

In: Blood, Vol. 100, No. 13, 15.12.2002, p. 4529-4536.

Research output: Contribution to journalArticle

Hall, Andrew Michael ; Ward, Frank James ; Vickers, Mark Adrian ; Stott, Lisa-Marie ; Urbaniak, Stanislaw ; Barker, Robert Norman. / Interleukin-10-mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen. In: Blood. 2002 ; Vol. 100, No. 13. pp. 4529-4536.
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AB - Regulatory T cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-gamma or to secrete the regulatory cytokine interleukin 10 when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4(+) phenotype. Serial results from individual patients demonstrated that this bias toward proliferative or interleukin-10 responses was unstable over time and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin 10 and dependent on cytotonic T lymphocyte-associated antigen (CTLA-4) costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease.

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