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CD4(+)CD25(-)Nrp1(+) T cells synergize with rapamycin to prevent murine cardiac allorejection in immunocompetent recipients
- Source :
- PLoS ONE, Vol 8, Iss 4, p e61151 (2013), PLoS ONE, 8(4). Public Library of Science, PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Besides CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), other immunosuppressive T cells also participated in the regulation of immune tolerance. Reportedly, neuropilin-1 (Nrp1) might be one of the molecules by which regulatory cells exert their suppressive effects. Indeed, CD4(+)CD25(-)Nrp1(+) T cells exhibit potent suppressive function in autoimmune inflammatory responses. Here we investigated the specific role of CD4(+)CD25(-)Nrp1(+) T cells in the setting of the transplant immune response. Through MLR assays, we found that CD4(+)CD25(+)Nrp1(+) T cells suppressed the proliferation of naive CD4(+)CD25(-) T cells activated by allogeneic antigen-stimulation. Adoptive transfer of CD4(+)CD25(-)Nrp1(+) T cells synergized with rapamycin to induce long-term graft survival in fully MHC-mismatched murine heart transplantation, which was associated with decreased IFN-gamma, IL-17 and increased IL-10, TGF-beta, Foxp3 and Nrp1 expression in the grafts. Importantly, our data indicated that CD4(+)CD25(-)Nrp1(+) T cell transfer augments the accumulation of Tregs in the recipient, and creates conditions that favored induction of hyporesponsiveness of the T effector cells. In conclusion, this translational study indicates the possible therapeutic potential of CD4(+)CD25(-)Nrp1(+) T cells in preventing allorejection. CD4(+)Nrp1(+) T cells might therefore be used in bulk as a population of immunosuppressive cells with more beneficial properties concerning ex vivo isolation as compared to Foxp3(+) Tregs
- Subjects :
- CD4-Positive T-Lymphocytes
Graft Rejection
Mouse
lcsh:Medicine
Cell Separation
Adaptive Immunity
T-Lymphocytes, Regulatory
Interleukin 21
Mice
Cytotoxic T cell
IL-2 receptor
lcsh:Science
Immune Response
Multidisciplinary
T Cells
Statistics
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Animal Models
Natural killer T cell
Adoptive Transfer
medicine.anatomical_structure
Transplant Surgery
Medicine
Cytokines
Immunocompetence
Research Article
T cell
Immune Cells
Immunology
chemical and pharmacologic phenomena
Biology
Biostatistics
Immune Suppression
Immunomodulation
Model Organisms
medicine
Immune Tolerance
Animals
Antigen-presenting cell
Interleukin 3
Sirolimus
Transplantation
lcsh:R
Immunity
Interleukin-2 Receptor alpha Subunit
Immunologic Subspecialties
Neuropilin-1
Heart Transplantation
Clinical Immunology
Surgery
lcsh:Q
Mathematics
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....686f209bde934d121ccdbf49cb848b7d