PMID- 17198269 OWN - NLM STAT- MEDLINE DCOM- 20070227 LR - 20171116 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 82 IP - 12 DP - 2006 Dec 27 TI - Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: Potential reagents to promote donor-specific transplantation tolerance. PG - 1738-43 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. FAU - Jiang, Shuiping AU - Jiang S AD - Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London, United Kingdom. shuiping.jiang@kcl.ac.uk FAU - Tsang, Julia AU - Tsang J FAU - Game, David S AU - Game DS FAU - Stevenson, Saskia AU - Stevenson S FAU - Lombardi, Giovanna AU - Lombardi G FAU - Lechler, Robert I AU - Lechler RI LA - eng PT - Journal Article PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (CD4 Antigens) RN - 0 (HLA A2 (103-120) peptide, human) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A2 Antigen) RN - 0 (HLA-DRB1 Chains) RN - 0 (HLA-DRB1*01:01 antigen) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - 0 (Peptide Fragments) SB - IM MH - Animals MH - CD4 Antigens/analysis MH - *Cell Culture Techniques MH - Dendritic Cells/immunology MH - HLA-A Antigens/immunology MH - HLA-A2 Antigen/chemistry/*immunology/pharmacology MH - HLA-DRB1 Chains MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Interleukin-2 Receptor alpha Subunit/analysis MH - Mice MH - Peptide Fragments/chemistry/immunology/pharmacology MH - T-Lymphocytes, Regulatory/drug effects/*immunology/transplantation MH - Tissue Donors MH - *Transplantation Tolerance EDAT- 2007/01/02 09:00 MHDA- 2007/02/28 09:00 CRDT- 2007/01/02 09:00 PHST- 2007/01/02 09:00 [pubmed] PHST- 2007/02/28 09:00 [medline] PHST- 2007/01/02 09:00 [entrez] AID - 00007890-200612270-00040 [pii] AID - 10.1097/01.tp.0000244932.29542.9e [doi] PST - ppublish SO - Transplantation. 2006 Dec 27;82(12):1738-43. doi: 10.1097/01.tp.0000244932.29542.9e.