Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: Potential reagents to promote donor-specific transplantation tolerance

TY - JOUR

T1 - Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity

T2 - Potential reagents to promote donor-specific transplantation tolerance

AU - Jiang, Shuiping

AU - Tsang, Julia

AU - Game, David S

AU - Stevenson, Saskia

AU - Lombardi, Giovanna

AU - Lechler, Robert I

PY - 2006/12/27

Y1 - 2006/12/27

N2 - 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.

AB - 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.

U2 - 10.1097/01.tp.0000244932.29542.9e

DO - 10.1097/01.tp.0000244932.29542.9e

M3 - Article

C2 - 17198269

VL - 82

SP - 1738

EP - 1743

JO - Transplantation

JF - Transplantation

IS - 12

ER -