Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells.
Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a pre...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1797084654795227136 |
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| author | Mwangi, W Smith, L Baigent, S Beal, R Nair, V Smith, A |
| author_facet | Mwangi, W Smith, L Baigent, S Beal, R Nair, V Smith, A |
| author_sort | Mwangi, W |
| collection | OXFORD |
| description | Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both "public" and "private" CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation. |
| first_indexed | 2024-03-07T01:58:05Z |
| format | Journal article |
| id | oxford-uuid:9c6adefb-8031-4d81-9743-21e264cf621d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:58:05Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:9c6adefb-8031-4d81-9743-21e264cf621d2022-03-27T00:35:51ZClonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9c6adefb-8031-4d81-9743-21e264cf621dEnglishSymplectic Elements at Oxford2011Mwangi, WSmith, LBaigent, SBeal, RNair, VSmith, ALymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both "public" and "private" CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation. |
| spellingShingle | Mwangi, W Smith, L Baigent, S Beal, R Nair, V Smith, A Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells. |
| title | Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells. |
| title_full | Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells. |
| title_fullStr | Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells. |
| title_full_unstemmed | Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells. |
| title_short | Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells. |
| title_sort | clonal structure of rapid onset mdv driven cd4 lymphomas and responding cd8 t cells |
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