Role of reentry of in vivo alloMHC peptide-activated T cells into the adult thymus in acquired systemic tolerance
| Autor: | R, Gopinathan, H A, DePaz, O O, Oluwole, A O, Ali, M, Garrovillo, K, Engelstad, M A, Hardy, S F, Oluwole |
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| Rok vydání: | 2001 |
| Předmět: |
T-Lymphocytes
Indium Radioisotopes Rats Inbred WF Dendritic Cells Thymus Gland Lymphocyte Activation Oxyquinoline Adoptive Transfer Rats Rats Inbred ACI Major Histocompatibility Complex Kinetics Transplantation Isogeneic Immune Tolerance Organometallic Compounds Animals Transplantation Homologous Spleen |
| Zdroj: | Transplantation. 72(9) |
| ISSN: | 0041-1337 |
| Popis: | T cell recognition of alloMHC peptide presented by self dendritic cells via the indirect pathway of allorecognition in the thymus induces T cell tolerance. Most recently we have shown that the i.v. administration of immunodominant Wistar Furth MHC class I (RT1.Au) peptide 5- (P5) pulsed myeloid or lymphoid dendritic cells induces operational tolerance to a fully MHC-mismatched cardiac allograft. This finding led us to hypothesize that circulation of peripheral P5-activated T cells to the thymus plays an important role in the induction of acquired tolerance.We used the adoptive transfer of 111Indium-oxine- (111In-oxine) labeled P5-pulsed syngeneic dendritic cells and in vivo P5-activated syngeneic T cells to study the role of their circulation to the thymus in the induction of transplantation tolerance.Intravenously administered 111In-oxine-labeled naïve DC actively migrated to and localized in the liver and spleen but did not enter the lymph nodes, bone marrow, and thymus. In vitro peptide-pulsed dendritic cells had a similar pattern of tissue localization except for a modest number of myeloid but not lymphoid DC entering the thymus. The demonstration that adoptive transfer of in vivo peptide-primed T cells induces permanent graft survival in antilymphocyte serum transiently immunosuppressed syngeneic secondary hosts led us to examine the traffic of in vivo activated T cells. Whereas naïve syngeneic T cells preferentially homed to the peripheral lymphoid organs, they did not reenter the thymus. In contrast, in vivo peptide-activated peripheral T cells migrated to and accumulated in the thymus, thus confirming that reentry of T cells to the thymus is restricted to in vivo activated T cells. Although antilymphocyte serum immunosuppression significantly reduced circulation of primed T cells to the thymus, it did not completely abolish it, as seen with gamma-irradiated primed T cells.These findings provide the first formal evidence directly linking reentry of in vivo alloMHC peptide-activated T cells to the thymus with the induction and possibly maintenance of acquired antigen-specific tolerance. Our results suggest that the thymus is open to a two-way traffic with the periphery and may function as a repository of immunological memory. |
| Databáze: | OpenAIRE |
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