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Critical influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression
- Source :
- Transplantation, 79 (6
- Publication Year :
- 2005
-
Abstract
- BACKGROUND: Allografts are occasionally accepted in the absence of immunosuppression. Because naturally occurring CD4(+)CD25(+) regulatory T cells (natural CD25(+) Treg cells) have been shown to inhibit allograft rejection, we investigated their influence on the outcome of allografts in nonimmunosuppressed mouse recipients. METHODS: We compared survival times of male CBA/Ca skin grafts in female CBA/Ca recipients expressing a transgenic anti-HY T-cell receptor on a RAG-1(+/+) (A1[M]RAG+) or a RAG-1(-/-) (A1[M]RAG-) background. Depletion of natural CD25(+) Treg cells in A1[M]RAG+ mice was achieved by in vivo administration of the PC61 monoclonal antibody. The influence of natural CD25(+) Treg cells on the fate of major histocompatibility complex class II-mismatched (C57BL/6X bm12)F1 skin or bm12 heart transplants in C57BL/6 recipients was also assessed. Finally, we investigated the impact of natural CD25(+) Treg cells on the production of T-helper (Th)1 and Th2 cytokines in mixed lymphocyte cultures between C57BL/6 CD4(+) CD25(-) T cells as responders and bm12 or (C57BL/6X bm12)F1 antigen-presenting cells as stimulators. RESULTS: Male allografts were spontaneously accepted by female A1(M)RAG+ mice but readily rejected by female A1(M)RAG+ mice depleted of natural CD25(+) Treg cells by pretreatment with the PC61 monoclonal antibody. Depletion of CD25(+) Treg cells also enhanced eosinophil-determined rejection of (C57BL/6X bm12)F1 skin grafts or bm12 cardiac grafts in C57BL/6 recipients. Finally, natural CD25(+) Treg cells inhibited the production of interleukin (IL)-2, interferon-gamma, IL-5, and IL-13 in mixed lymphocyte culture in a dose-dependent manner. CONCLUSION: Natural CD25(+) Treg cells control Th1- and Th2-type allohelper T-cell responses and thereby influence the fate of allografts in nonimmunosuppressed recipients.<br />Journal Article<br />Research Support, Non-U.S. Gov't<br />info:eu-repo/semantics/published
- Subjects :
- Graft Rejection
Male
medicine.medical_treatment
Lymphocyte
T-Lymphocytes
Transplantation, Homologous -- immunology
Mice
Allograft
IL-2 receptor
Receptor
Th2 Cells -- immunology
Graft Survival
Th2 Cells -- metabolism
Interleukin
Immunosuppression
hemic and immune systems
Skin Transplantation
Sciences bio-médicales et agricoles
Cytokines -- immunology
Cytokines -- metabolism
medicine.anatomical_structure
Skin Transplantation -- immunology
Cytokines
Female
Graft Rejection -- immunology
Receptors, Interleukin-2 -- metabolism
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell -- immunology
chemical and pharmacologic phenomena
Mice, Transgenic
Biology
Major histocompatibility complex
Heart Transplantation -- immunology
Immune system
Th2 Cells
medicine
Transplantation, Homologous
Animals
Receptors, Interleukin-2 -- immunology
Skin Transplantation -- pathology
Th1 Cells -- metabolism
T-Lymphocytes -- metabolism
Immunosuppression Therapy
Transplantation
Heart Transplantation -- pathology
Receptors, Interleukin-2
T lymphocyte
Th1 Cells
Graft Survival -- immunology
Rats
Mice, Inbred C57BL
Receptors, Antigen, T-Cell -- genetics
Immunology
biology.protein
Heart Transplantation
T-Lymphocytes -- immunology
Lymphocyte Culture Test, Mixed
Th1 Cells -- immunology
Regulatory T cell
Tolerance
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Transplantation, 79 (6
- Accession number :
- edsair.doi.dedup.....9dbd4aa3b035c17602e1a04aee19acbb