PMID- 17174746 OWN - NLM STAT- MEDLINE DCOM- 20070202 LR - 20061218 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 67 IP - 12 DP - 2006 Dec TI - Human bone marrow stromal cells hamper specific interactions of CD4 and CD8 T lymphocytes with antigen-presenting cells. PG - 976-85 AB - Bone marrow stromal cells (BMSCs) may inhibit T-cell functions in vitro and thus have been proposed as immunoregulators to control in vivo graft-versus-host disease (GVHD) in haploidentical hemopoietic stem cell transplants. To better investigate this phenomenon, we used a defined experimental system in which responding T cells are antigen-specific and devoid of alloreactivity against BMSC from a different subject. Thus, we established antigen-specific human CD4 and CD8 T-cell lines as the readout system. Antigen-dependent proliferation was reduced with both T-cell subsets cultured on confluent BMSCs, and also on confluent human skin fibroblasts (HSF) inhibited T-cell proliferation with similar efficiency. Morphological observations of the cocultures showed impairment of physical interactions between T-cell and antigen-presenting cells in the presence of BMSC, with lack of formation of antigen-dependent clusters of T cells and antigen-presenting cells (APCs). In contrast, no effects were seen with BMSC-conditioned medium. Since suppression was seen only with confluent mesenchymal cells, this phenomenon may not be relevant in vivo, where BMSCs are at low frequency. In addition, if the reported suppressive effect of BMSCs on GVHD in vivo is confirmed, a different in vitro system should be envisaged to better understand and exploit the underlying mechanism. FAU - Li Pira, Giuseppina AU - Li Pira G AD - Advanced Biotechnology Center, Genoa, Italy. lipira@email.it FAU - Ivaldi, Federico AU - Ivaldi F FAU - Bottone, Laura AU - Bottone L FAU - Quarto, Rodolfo AU - Quarto R FAU - Manca, Fabrizio AU - Manca F LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061018 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 SB - IM MH - Adolescent MH - Adult MH - Antigen-Presenting Cells/*immunology MH - Bone Marrow Cells/*immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Cell Communication/*immunology MH - Cell Line MH - Child MH - Child, Preschool MH - Coculture Techniques MH - Graft vs Host Disease/*immunology MH - Hematopoietic Stem Cell Transplantation MH - Humans MH - Male MH - Middle Aged MH - Stromal Cells/immunology MH - Transplantation, Homologous EDAT- 2006/12/19 09:00 MHDA- 2007/02/03 09:00 CRDT- 2006/12/19 09:00 PHST- 2006/01/26 00:00 [received] PHST- 2006/07/12 00:00 [revised] PHST- 2006/08/17 00:00 [accepted] PHST- 2006/12/19 09:00 [pubmed] PHST- 2007/02/03 09:00 [medline] PHST- 2006/12/19 09:00 [entrez] AID - S0198-8859(06)00481-2 [pii] AID - 10.1016/j.humimm.2006.08.298 [doi] PST - ppublish SO - Hum Immunol. 2006 Dec;67(12):976-85. doi: 10.1016/j.humimm.2006.08.298. Epub 2006 Oct 18.