Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection.
Regulatory T cells (Treg) have been shown to play a role in the prevention of autoimmune diseases and transplant rejection. Based on an established protocol known to generate alloantigen reactive Treg in vivo, we have developed a strategy for the in vitro selection of Treg. Stimulation of unfraction...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1797067636346978304 |
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| author | Oliveira, V Sawitzki, B Chapman, S Appelt, C Gebuhr, I Wieckiewicz, J Long, E Wood, K |
| author_facet | Oliveira, V Sawitzki, B Chapman, S Appelt, C Gebuhr, I Wieckiewicz, J Long, E Wood, K |
| author_sort | Oliveira, V |
| collection | OXFORD |
| description | Regulatory T cells (Treg) have been shown to play a role in the prevention of autoimmune diseases and transplant rejection. Based on an established protocol known to generate alloantigen reactive Treg in vivo, we have developed a strategy for the in vitro selection of Treg. Stimulation of unfractionated CD4(+) T cells from naive CBA.Ca (H2(k)) mice with C57BL/10 (H2(b)) splenocytes in the presence of an anti-CD4 antibody, YTS 177, resulted in the selection of Treg able to inhibit proliferation of naive T cells. In vivo, the cells were able to prevent rejection of 80% C57BL/10 skin grafts when co-transferred to CBA.Rag(-/-) mice together with naive CD45RB(high)CD4(+) cells. Purification of CD62L(+)CD25(+)CD4(+) cells from the cultures enriched for cells with regulatory activity; as now 100% survival of C57BL/10 skin grafts was achieved. Furthermore, differentiation of Treg could be also achieved when using purified CD25(-)CD4(+) naive T cells as a starting population. Interestingly, further in vitro expansion resulted in a partial loss of CD4(+) cells expressing both CD62L and CD25 and abrogation of their regulatory activity in vivo. This study shows that alloantigen stimulation in the presence of anti-CD4 in vitro provides a simple and effective strategy to generate alloreactive Treg. |
| first_indexed | 2024-03-06T21:59:11Z |
| format | Journal article |
| id | oxford-uuid:4e01b58f-1b47-49d5-942a-e9b4a9d2b90b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:59:11Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:4e01b58f-1b47-49d5-942a-e9b4a9d2b90b2022-03-26T15:58:39ZAnti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e01b58f-1b47-49d5-942a-e9b4a9d2b90bEnglishSymplectic Elements at Oxford2008Oliveira, VSawitzki, BChapman, SAppelt, CGebuhr, IWieckiewicz, JLong, EWood, KRegulatory T cells (Treg) have been shown to play a role in the prevention of autoimmune diseases and transplant rejection. Based on an established protocol known to generate alloantigen reactive Treg in vivo, we have developed a strategy for the in vitro selection of Treg. Stimulation of unfractionated CD4(+) T cells from naive CBA.Ca (H2(k)) mice with C57BL/10 (H2(b)) splenocytes in the presence of an anti-CD4 antibody, YTS 177, resulted in the selection of Treg able to inhibit proliferation of naive T cells. In vivo, the cells were able to prevent rejection of 80% C57BL/10 skin grafts when co-transferred to CBA.Rag(-/-) mice together with naive CD45RB(high)CD4(+) cells. Purification of CD62L(+)CD25(+)CD4(+) cells from the cultures enriched for cells with regulatory activity; as now 100% survival of C57BL/10 skin grafts was achieved. Furthermore, differentiation of Treg could be also achieved when using purified CD25(-)CD4(+) naive T cells as a starting population. Interestingly, further in vitro expansion resulted in a partial loss of CD4(+) cells expressing both CD62L and CD25 and abrogation of their regulatory activity in vivo. This study shows that alloantigen stimulation in the presence of anti-CD4 in vitro provides a simple and effective strategy to generate alloreactive Treg. |
| spellingShingle | Oliveira, V Sawitzki, B Chapman, S Appelt, C Gebuhr, I Wieckiewicz, J Long, E Wood, K Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection. |
| title | Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection. |
| title_full | Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection. |
| title_fullStr | Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection. |
| title_full_unstemmed | Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection. |
| title_short | Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection. |
| title_sort | anti cd4 mediated selection of treg in vitro in vitro suppression does not predict in vivo capacity to prevent graft rejection |
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