Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: Potential reagents to promote donor-specific transplantation tolerance.
Transplantation
; 82(12): 1738-43, 2006 Dec 27.
Article
em En
| MEDLINE
| ID: mdl-17198269
ABSTRACT
BACKGROUND:
Harnessing naturally arising CD4+ CD25+ regulatory T cells (Tregs) for potential adoptive cell therapy is hampered by their innate autoreactivity and their limited number.METHODS:
CD4+ CD25+ Tregs were purified from peripheral blood of human leukocyte antigen (HLA) DR1*0101+ A2- individuals, and stimulated with autologous monocyte-derived dendritic cells (DCs).RESULTS:
Here we show that CD4+ CD25+ Tregs specific for an HLA A2 (103-120) peptide can be selected from the peripheral blood CD4+ CD25+ T cell population of a healthy individual and detected using a tetramer comprised of HLA DRB1*0101 and the A2 peptide. The selected cells can be expanded substantially (i.e., a 1600-fold increase over a two-week period) by T-cell receptor (TCR) stimulation and high-doses of interleukin-2 (IL-2). The CD4+ CD25+Tregs with indirect allospecificity for the A2 peptide showed more potent antigen-specific suppression than polyclonal CD4+ CD25+ Tregs.CONCLUSIONS:
These data may pave the way for clinical studies using CD4+ CD25+ Tregs with indirect allospecificity as therapeutic reagents for the induction of donor-specific transplantation tolerance.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígeno HLA-A2
/
Imunoterapia Adotiva
/
Linfócitos T Reguladores
/
Técnicas de Cultura de Células
/
Tolerância ao Transplante
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Transplantation
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido