Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: Potential reagents to promote donor-specific transplantation tolerance
S Jiang, J Tsang, DS Game, S Stevenson… - …, 2006 - journals.lww.com
S Jiang, J Tsang, DS Game, S Stevenson, G Lombardi, RI Lechler
Transplantation, 2006•journals.lww.comBackground. Harnessing naturally arising CD4+ CD25+ regulatory T cells (T regs) for
potential adoptive cell therapy is hampered by their innate autoreactivity and their limited
number. Methods. CD4+ CD25+ T regs 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+ T regs
specific for an HLA A2 (103–120) peptide can be selected from the peripheral blood CD4+ …
potential adoptive cell therapy is hampered by their innate autoreactivity and their limited
number. Methods. CD4+ CD25+ T regs 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+ T regs
specific for an HLA A2 (103–120) peptide can be selected from the peripheral blood CD4+ …
Abstract
Background.
Harnessing naturally arising CD4+ CD25+ regulatory T cells (T regs) for potential adoptive cell therapy is hampered by their innate autoreactivity and their limited number.
Methods.
CD4+ CD25+ T regs 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+ T regs 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 (ie, 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+ T regs with indirect allospecificity for the A2 peptide showed more potent antigen-specific suppression than polyclonal CD4+ CD25+ T regs.
Conclusions.
These data may pave the way for clinical studies using CD4+ CD25+ T regs with indirect allospecificity as therapeutic reagents for the induction of donor-specific transplantation tolerance.
Lippincott Williams & Wilkins