Adoptive transfer of freshly isolated natural occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) prevents graft-versus-host disease (GVHD) in several animal models and following hematopoietic cell transplantation (HCT) in clinical trials. Donor-derived Treg have been mainly used, as they share the same MHC with CD4(+) and CD8(+) conventional T cells (Tcon) that are primarily responsible for GVHD. Third party-derived Treg are a promising alternative for cellular therapy, as they can be prepared in advance, screened for pathogens and activity, and banked. We explored MHC disparities between Treg and Tcon in HCT to evaluate the impact of different Treg populations in GVHD prevention and survival. Third-party Treg and donor Treg are equally suppressive in ex vivo assays, whereas both donor and third-party but not host Treg protect from GVHD in allogeneic HCT, with donor Treg being the most effective. In an MHC minor mismatched transplantation model (C57BL/6 → BALB/b), donor and third-party Treg were equally effective in controlling GVHD. Furthermore, using an in vivo Treg depletion mouse model, we found that Treg exert their main suppressive activity in the first 2 d after transplantation. Third-party Treg survive for a shorter period of time after adoptive transfer, but despite the shorter survival, they control Tcon proliferation in the early phases of HCT. These studies provide relevant insights on the mechanisms of Treg-mediated protection from GVHD and support for the use of third-party Treg in clinical trials.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475671 | PMC |
| http://dx.doi.org/10.4049/jimmunol.1402861 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Propionic acid supplementation promotes the expansion of regulatory T cells in patients with end-stage renal disease but not in renal transplant patients.
Front Transplant
September 2024
Clinic for Internal Medicine, St. Anna Hospital Herne, Herne, Germany.
Article Synopsis
- The study investigates the effects of propionic acid on inflammation and T-cell composition in kidney transplant patients compared to dialysis patients.
- A total of 26 participants (10 dialysis and 16 transplant patients) received propionic acid supplementation for 30 days while their immune systems were analyzed before, after, and during follow-ups.
- Results showed that propionic acid enhanced Treg expansion in dialysis patients but had no significant effect on Treg levels in transplant patients, likely due to the immunosuppressive therapy they were undergoing.
Nanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen.
Front Immunol
August 2024
Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
We have previously reported that nanoparticles (NPs) loaded with IL-2 and TGF-β and targeted to T cells induced polyclonal T regulatory cells (Tregs) that protected mice from graft-versus-host disease (GvHD). Here, we evaluated whether administration of these NPs during alloantigen immunization could prevent allograft rejection by converting immunogenic responses to tolerogenic ones. Using C57BL/6 mice and BALB/c mice as either donors or recipients of allogeneic splenocytes, we found that treatment with the tolerogenic NPs in both strains of mice resulted in a marked inhibition of mixed lymphocyte reaction (MLR) to donor cell alloantigen but not to third-party control mouse cells after transfer of the allogeneic cells.
View Article and Find Full Text PDFMyeloid-derived suppressor cells promote allograft survival by suppressing regulatory T cell dysfunction in high-risk corneal transplantation.
Am J Transplant
September 2024
Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:
Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6-mediated Treg dysfunction by expressing interleukin-10.
View Article and Find Full Text PDFHighly purified and functionally stable expanded allospecific Tr1 cells expressing immunosuppressive graft-homing receptors as new candidates for cell therapy in solid organ transplantation.
Front Immunol
March 2023
Department of Immunology, Biomedical Research Institute, Mexico City, Mexico.
The development of new strategies based on the use of Tr1 cells has taken relevance to induce long-term tolerance, especially in the context of allogeneic stem cell transplantation. Although Tr1 cells are currently identified by the co-expression of CD49b and LAG-3 and high production of interleukin 10 (IL-10), recent studies have shown the need for a more exhaustive characterization, including co-inhibitory and chemokines receptors expression, to ensure bona fide Tr1 cells to be used as cell therapy in solid organ transplantation. Moreover, the proinflammatory environment induced by the allograft could affect the suppressive function of Treg cells, therefore stability of Tr1 cells needs to be further investigated.
View Article and Find Full Text PDFTransplant Tolerance, Not Only Clonal Deletion.
Front Immunol
May 2022
Immune Tolerance Laboratory, School of Medicine, University of New South Wales (UNSW) Sydney, Ingham Institute, and Renal Service and Multiple Sclerosis Clinic, Liverpool Hospital, Liverpool, NSW, Australia.
The quest to understand how allogeneic transplanted tissue is not rejected and how tolerance is induced led to fundamental concepts in immunology. First, we review the research that led to the Clonal Deletion theory in the late 1950s that has since dominated the field of immunology and transplantation. At that time many basic mechanisms of immune response were unknown, including the role of lymphocytes and T cells in rejection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!