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 language | English |
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Pages (from-to) | 4529-4536 |
Number of pages | 8 |
Journal | Blood |
Volume | 100 |
Issue number | 13 |
DOIs | |
Publication status | Published - 15 Dec 2002 |
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