Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells.
BACKGROUND: Intravenous immunoglobulins (IVIg) therapy is effective as a treatment for T-cell-mediated immune diseases, but whether and how IVIg suppress allogeneic T-cell responses is largely unknown. METHODS: In vitro, human CD4(+), CD4(+)CD25(-), or CD4(+)CD25(+) T cells were stimulated with all...
| Asıl Yazarlar: | , , , , |
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| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
2010
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| _version_ | 1826292007803289600 |
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| author | Tha-In, T Metselaar, H Bushell, A Kwekkeboom, J Wood, K |
| author_facet | Tha-In, T Metselaar, H Bushell, A Kwekkeboom, J Wood, K |
| author_sort | Tha-In, T |
| collection | OXFORD |
| description | BACKGROUND: Intravenous immunoglobulins (IVIg) therapy is effective as a treatment for T-cell-mediated immune diseases, but whether and how IVIg suppress allogeneic T-cell responses is largely unknown. METHODS: In vitro, human CD4(+), CD4(+)CD25(-), or CD4(+)CD25(+) T cells were stimulated with allogeneic antigen-presenting cells (APCs), and mouse CBA/Ca (H2(k)) CD4(+) or CD4(+)CD25(-) T cells were stimulated with C57BL/10 (H2(b)) splenocytes, in the presence or absence of IVIg. Proliferation, binding of IVIg, expression of activation markers, and ZAP70-phosphorylation were determined. In vivo, 1x10(5) CD4(+) or CD4(+)CD25(-) T cells of CBA/Ca mice were adoptively transferred into CBA/RAG1(-/-) mice, which were 1 day later transplanted with skin grafts of C57BL/10 mice. IVIg was administered intravenously and skin graft survival was determined. RESULTS: IVIg bound to the surface of human and mouse CD4(+)Foxp3(+) regulatory T cells (Tregs). IVIg binding resulted in functional activation of Tregs, as detected by increased expression of surface activation markers, enhanced ZAP70-phosphorylation, and increased capacity to suppress allogeneic T-cell proliferation. IVIg inhibited allogeneic T-cell proliferation in the presence of Tregs, but this effect was abrogated on selective depletion of CD25(+) cells from responder T cells. IVIg prevented T-cell-mediated rejection of fully mismatched skin grafts in CBA/RAG1(-/-) mice reconstituted with CD4(+) T cells, but this effect was lost on selective depletion of CD4(+)CD25(+) cells from transferred T cells, indicating that IVIg induced dominant allograft protection mediated by Tregs. CONCLUSIONS: Our data show that IVIg suppress allogeneic T-cell responses by direct activation of Tregs. IVIg treatment, which has been proven safe, may have therapeutic potential in tolerance-inducing strategies in transplant medicine. |
| first_indexed | 2024-03-07T03:08:05Z |
| format | Journal article |
| id | oxford-uuid:b33ec37a-92c5-452a-a0e3-2661239ae00a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:08:05Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:b33ec37a-92c5-452a-a0e3-2661239ae00a2022-03-27T04:17:32ZIntravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b33ec37a-92c5-452a-a0e3-2661239ae00aEnglishSymplectic Elements at Oxford2010Tha-In, TMetselaar, HBushell, AKwekkeboom, JWood, K BACKGROUND: Intravenous immunoglobulins (IVIg) therapy is effective as a treatment for T-cell-mediated immune diseases, but whether and how IVIg suppress allogeneic T-cell responses is largely unknown. METHODS: In vitro, human CD4(+), CD4(+)CD25(-), or CD4(+)CD25(+) T cells were stimulated with allogeneic antigen-presenting cells (APCs), and mouse CBA/Ca (H2(k)) CD4(+) or CD4(+)CD25(-) T cells were stimulated with C57BL/10 (H2(b)) splenocytes, in the presence or absence of IVIg. Proliferation, binding of IVIg, expression of activation markers, and ZAP70-phosphorylation were determined. In vivo, 1x10(5) CD4(+) or CD4(+)CD25(-) T cells of CBA/Ca mice were adoptively transferred into CBA/RAG1(-/-) mice, which were 1 day later transplanted with skin grafts of C57BL/10 mice. IVIg was administered intravenously and skin graft survival was determined. RESULTS: IVIg bound to the surface of human and mouse CD4(+)Foxp3(+) regulatory T cells (Tregs). IVIg binding resulted in functional activation of Tregs, as detected by increased expression of surface activation markers, enhanced ZAP70-phosphorylation, and increased capacity to suppress allogeneic T-cell proliferation. IVIg inhibited allogeneic T-cell proliferation in the presence of Tregs, but this effect was abrogated on selective depletion of CD25(+) cells from responder T cells. IVIg prevented T-cell-mediated rejection of fully mismatched skin grafts in CBA/RAG1(-/-) mice reconstituted with CD4(+) T cells, but this effect was lost on selective depletion of CD4(+)CD25(+) cells from transferred T cells, indicating that IVIg induced dominant allograft protection mediated by Tregs. CONCLUSIONS: Our data show that IVIg suppress allogeneic T-cell responses by direct activation of Tregs. IVIg treatment, which has been proven safe, may have therapeutic potential in tolerance-inducing strategies in transplant medicine. |
| spellingShingle | Tha-In, T Metselaar, H Bushell, A Kwekkeboom, J Wood, K Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells. |
| title | Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells. |
| title_full | Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells. |
| title_fullStr | Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells. |
| title_full_unstemmed | Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells. |
| title_short | Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+Foxp3+ T cells. |
| title_sort | intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of cd4 foxp3 t cells |
| work_keys_str_mv | AT thaint intravenousimmunoglobulinspromoteskinallograftacceptancebytriggeringfunctionalactivationofcd4foxp3tcells AT metselaarh intravenousimmunoglobulinspromoteskinallograftacceptancebytriggeringfunctionalactivationofcd4foxp3tcells AT bushella intravenousimmunoglobulinspromoteskinallograftacceptancebytriggeringfunctionalactivationofcd4foxp3tcells AT kwekkeboomj intravenousimmunoglobulinspromoteskinallograftacceptancebytriggeringfunctionalactivationofcd4foxp3tcells AT woodk intravenousimmunoglobulinspromoteskinallograftacceptancebytriggeringfunctionalactivationofcd4foxp3tcells |