Mesenchymal stromal cells augment CD4+ and CD8+ T-cell proliferation through a CCL2 pathway |
| |
| Authors: | Yingzhe Zhou Andrea Day Siba Haykal Armand Keating Thomas K. Waddell |
| |
| Affiliation: | 1. Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, Toronto, Ontario, Canada;2. Cell Therapy Program, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada;1. Centre for Neuroscience Studies, Queen''s University, Kingston, Ontario, Canada;2. Department of Anesthesiology, Queen''s University, Kingston, Ontario, Canada;3. Department of Biomedical and Molecular Sciences, Queen''s University, Kingston, Ontario, Canada;1. Hematology and Stem Cell Transplantation Section, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA;2. Vanderbilt Asthma, Sinus, and Allergy Program (VASAP), Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA;3. Pediatric Stem Cell Transplant Program, Monroe Carell Jr. Children''s Hospital Vanderbilt University Medical Center, Nashville, Tennessee, USA;1. Dongguk University Research Institute of Biotechnology, Dongguk University, 3-26, Pil Dong, Choong-Gu, Seoul 100-715, Republic of Korea;2. School of Life Sciences and Biotechnology, Korea University, 1-5, Anam Dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea;1. Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany;2. Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Freiburg, Germany;1. Department of Hepatobiliary Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People''s Republic of China;2. Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People''s Republic of China;3. Department of Pathology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People''s Republic of China |
| |
| Abstract: | Background aimsMesenchymal stromal cells (MSC) derived from bone marrow are immunosuppressive in vitro and in vivo. Recent evidence, however, has shown that in certain settings, MSC can also be immunostimulatory. The mechanisms involved in this process are largely unknown.MethodsMouse spleen T cells were stimulated with allogeneic mixed lymphocyte reaction (MLR) or anti-CD3/CD28 beads and treated with autologous bone marrow MSC or MSC-conditioned medium. CD4+ and CD8+ T-cell proliferation was analyzed after treatment.ResultsWe show that MSC have both suppressive and stimulatory functions toward T cells after stimulation with anti-CD3/CD28 beads or in an MLR. This depended on the ratio of MSC to responder T cells, with low numbers of MSC increasing and higher numbers inhibiting T-cell proliferation. Immunostimulatory function was mediated, in part, by soluble factors. MSC immunosuppression of the MLR was indirect and related to inhibition of antigen-presenting cell maturation. Direct effects of MSC-conditioned medium during anti-CD3/CD28 stimulated proliferation were entirely stimulatory and required the presence of the T-cell receptor. MSC supernatant contained both CCL2 and CCL5 at high levels, but only CCL2 level correlated with the ability to augment proliferation. An anti-CCL2 antibody blocked this proliferative activity.ConclusionsCCL2 plays an important role in the immunostimulatory function of MSC, and we further hypothesize that the immunomodulatory role of MSC is determined by a balance between inhibitory and stimulatory factors, suggesting the need for caution when these cells are investigated in clinical protocols. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
