PMID- 18946352 OWN - NLM STAT- MEDLINE DCOM- 20081113 LR - 20181113 IS - 1534-6080 (Electronic) IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 86 IP - 8 DP - 2008 Oct 27 TI - Human inhibitory receptor immunoglobulin-like transcript 2 amplifies CD11b+Gr1+ myeloid-derived suppressor cells that promote long-term survival of allografts. PG - 1125-34 LID - 10.1097/TP.0b013e318186fccd [doi] AB - BACKGROUND: The expression of human leukocyte antigen (HLA)-G during allogeneic recognition is associated with better graft acceptance. The inhibitory receptor immunoglobulin-like transcript (ILT)-2 is expressed on activated T cells and serves to shut down T-cell activation, culminating in T-cell death, or induction of anergy. One of the potential mechanisms in the immunosuppressive accomplishment of HLA-G-ILT2 interactions involves the expansion of myeloid-derived suppressor cells (MDSCs). The potential of MDSCs in transplantation has not yet been exploited. METHODS: (1) Detailed phenotypic characteristics, immunosuppressive potential of MDSCs expanded by means of inhibitory receptor ILT2 and its ligands, and allogeneic transplant-activated MDSCs were obtained in mice. (2) Oligo- and real-time pathway-specific polymerase chain reaction arrays were performed to characterize ILT2-specific MDSCs. (3) Skin allograft survival after adoptive transfer of MDSCs was studied. RESULTS: Engagement of ILT2 receptors, especially by HLA-G, expanded the population of MDSCs with enhanced suppressive activity. Adoptive transfer of MDSCs generated by ILT2 receptor and its ligands prolonged graft survival in recipients of allogeneic skin transplant. We have proposed pathways for enhancement of immunosuppressive activities and expansion of MDSCs by ILT2 and HLA-G. CONCLUSIONS: Our results suggest that induction of MDSCs using ILT2 inhibitory receptor/HLA-G ligand may be an attractive strategy for preventing rejection of immunogenic organs or tissues in clinical transplantation. FAU - Zhang, Wei AU - Zhang W AD - Department of Medicine, Center for Molecular Chaperone/Radiobiology and Cancer Virology, Medical College of Georgia, Augusta, GA, USA. FAU - Liang, Siyuan AU - Liang S FAU - Wu, Juan AU - Wu J FAU - Horuzsko, Anatolij AU - Horuzsko A LA - eng GR - R01 AI055923/AI/NIAID NIH HHS/United States GR - R01 AI055923-04/AI/NIAID NIH HHS/United States GR - R01 AI055923-05/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Antigens, CD) RN - 0 (CD11b Antigen) RN - 0 (Gr-1 protein, mouse) RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (LILRB1 protein, human) RN - 0 (Leukocyte Immunoglobulin-like Receptor B1) RN - 0 (Ligands) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, Immunologic) SB - IM MH - Adoptive Transfer MH - Animals MH - Antigens, CD/genetics/*metabolism MH - CD11b Antigen/*metabolism MH - Cell Movement/immunology MH - *Cell Proliferation MH - Cells, Cultured MH - Graft Rejection/genetics/immunology/*prevention & control MH - Graft Survival/genetics/*immunology MH - HLA Antigens/metabolism MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/metabolism MH - Humans MH - *Immune Tolerance/genetics MH - Leukocyte Immunoglobulin-like Receptor B1 MH - Ligands MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Myeloid Cells/*immunology/transplantation MH - Phenotype MH - Receptors, Chemokine/*metabolism MH - Receptors, Immunologic/genetics/*metabolism MH - *Skin Transplantation MH - T-Lymphocytes/immunology MH - Time Factors MH - Transcription, Genetic MH - Transplantation, Homologous PMC - PMC2668611 MID - NIHMS84838 COIS- Conflict of interest disclosure: The authors declare no potential conflict of interest. EDAT- 2008/10/24 09:00 MHDA- 2008/11/14 09:00 PMCR- 2009/10/27 CRDT- 2008/10/24 09:00 PHST- 2008/10/24 09:00 [pubmed] PHST- 2008/11/14 09:00 [medline] PHST- 2008/10/24 09:00 [entrez] PHST- 2009/10/27 00:00 [pmc-release] AID - 00007890-200810270-00017 [pii] AID - 10.1097/TP.0b013e318186fccd [doi] PST - ppublish SO - Transplantation. 2008 Oct 27;86(8):1125-34. doi: 10.1097/TP.0b013e318186fccd.