Transgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice.
CD2 is a cell surface glycoprotein present on all T cells which has been shown to function as an adhesion and signaling molecule. Expressed early in T cell development, human CD2 (HCD2) has been suggested to play a role during thymopoiesis. However, the relevance of CD2 in T cell development has bee...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1996
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| _version_ | 1797071488155648000 |
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| author | Melton, E Sarner, N Torkar, M Van Der Merwe, P Russell, J Budd, R Mamalaki, C Tolaini, M Kioussis, D Zamoyska, R |
| author_facet | Melton, E Sarner, N Torkar, M Van Der Merwe, P Russell, J Budd, R Mamalaki, C Tolaini, M Kioussis, D Zamoyska, R |
| author_sort | Melton, E |
| collection | OXFORD |
| description | CD2 is a cell surface glycoprotein present on all T cells which has been shown to function as an adhesion and signaling molecule. Expressed early in T cell development, human CD2 (HCD2) has been suggested to play a role during thymopoiesis. However, the relevance of CD2 in T cell development has been called into question recently, as neither disruption of the CD2 gene nor anti-CD2 antibody treatment of fetal thymic organ cultures in mouse were shown to have any discernible consequences. We have expressed HCD2 at high levels in transgenic mice and found a profound effect of the transgene on thymocyte differentiation. Transgenic thymuses are considerably reduced in cell number as a consequence of increased apoptosis of double-positive (DP) thymocytes in the cortex. The remaining DP cells have up-regulated levels of T cell receptor (TCR) and are resistant to apoptosis mediated by administration of antigen. These effects are dependent on the cytoplasmic domain of HCD2, as mice expressing comparable levels of a tailless HCD2 transgene have a normal phenotype. The HCD2 cytoplasmic domain contains several regions of identity with mouse CD2 and can interact effciently with mouse intracellular signaling machinery. These results suggest there is considerable cross-talk between CD2 and TCR on developing thymocytes with consequences for the stimulation threshold of mature T cells. |
| first_indexed | 2024-03-06T22:53:59Z |
| format | Journal article |
| id | oxford-uuid:5fc2037a-c473-4c8d-8781-6b4ece1686fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:53:59Z |
| publishDate | 1996 |
| record_format | dspace |
| spelling | oxford-uuid:5fc2037a-c473-4c8d-8781-6b4ece1686fb2022-03-26T17:48:55ZTransgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5fc2037a-c473-4c8d-8781-6b4ece1686fbEnglishSymplectic Elements at Oxford1996Melton, ESarner, NTorkar, MVan Der Merwe, PRussell, JBudd, RMamalaki, CTolaini, MKioussis, DZamoyska, RCD2 is a cell surface glycoprotein present on all T cells which has been shown to function as an adhesion and signaling molecule. Expressed early in T cell development, human CD2 (HCD2) has been suggested to play a role during thymopoiesis. However, the relevance of CD2 in T cell development has been called into question recently, as neither disruption of the CD2 gene nor anti-CD2 antibody treatment of fetal thymic organ cultures in mouse were shown to have any discernible consequences. We have expressed HCD2 at high levels in transgenic mice and found a profound effect of the transgene on thymocyte differentiation. Transgenic thymuses are considerably reduced in cell number as a consequence of increased apoptosis of double-positive (DP) thymocytes in the cortex. The remaining DP cells have up-regulated levels of T cell receptor (TCR) and are resistant to apoptosis mediated by administration of antigen. These effects are dependent on the cytoplasmic domain of HCD2, as mice expressing comparable levels of a tailless HCD2 transgene have a normal phenotype. The HCD2 cytoplasmic domain contains several regions of identity with mouse CD2 and can interact effciently with mouse intracellular signaling machinery. These results suggest there is considerable cross-talk between CD2 and TCR on developing thymocytes with consequences for the stimulation threshold of mature T cells. |
| spellingShingle | Melton, E Sarner, N Torkar, M Van Der Merwe, P Russell, J Budd, R Mamalaki, C Tolaini, M Kioussis, D Zamoyska, R Transgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice. |
| title | Transgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice. |
| title_full | Transgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice. |
| title_fullStr | Transgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice. |
| title_full_unstemmed | Transgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice. |
| title_short | Transgene-encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice. |
| title_sort | transgene encoded human cd2 acts in a dominant negative fashion to modify thymocyte selection signals in mice |
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