T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice
| Autor: | Oldreive, C.E., Skowronska, A., Davies, N.J., Parry, H., Agathanggelou, A., Krysov, S., Packham, G., Rudzki, Z., Cronin, L., Vrzalikova, K., Murray, P., Odintsova, E., Pratt, G., Taylor, A.M., Moss, P., Stankovic, T. |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cytotoxicity
Immunologic Time Factors Cell Survival lcsh:Medicine Mice SCID CD8-Positive T-Lymphocytes Lymphocyte Activation Lymphocyte Depletion Mouse model Immunocompromised Host Lymphocytes Tumor-Infiltrating Mice Inbred NOD T-Lymphocyte Subsets hemic and lymphatic diseases lcsh:Pathology Tumor Microenvironment Animals Humans Cells Cultured Cell Proliferation lcsh:R Graft Survival Leukemia Lymphocytic Chronic B-Cell Coculture Techniques Phenotype T-cell depletion Heterografts CLL Neoplasm Transplantation Spleen lcsh:RB1-214 Research Article |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 8, Iss 11, Pp 1401-1412 (2015) |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | Chronic lymphocytic leukaemia (CLL) cells require microenvironmental support for their proliferation. This can be recapitulated in highly immunocompromised hosts in the presence of T cells and other supporting cells. Current primary CLL xenograft models suffer from limited duration of tumour cell engraftment coupled with gradual T-cell outgrowth. Thus, a greater understanding of the interaction between CLL and T cells could improve their utility. In this study, using two distinct mouse xenograft models, we investigated whether xenografts recapitulate CLL biology, including natural environmental interactions with B-cell receptors and T cells, and whether manipulation of autologous T cells can expand the duration of CLL engraftment. We observed that primary CLL xenografts recapitulated both the tumour phenotype and T-cell repertoire observed in patients and that engraftment was significantly shorter for progressive tumours. A reduction in the number of patient T cells that were injected into the mice to 2-5% of the initial number or specific depletion of CD8+ cells extended the limited xenograft duration of progressive cases to that characteristic of indolent disease. We conclude that manipulation of T cells can enhance current CLL xenograft models and thus expand their utility for investigation of tumour biology and pre-clinical drug assessment. Summary: Manipulation of T cells can enhance current CLL xenograft models, expanding their utility for investigation of tumour biology and pre-clinical drug assessment. |
| Databáze: | OpenAIRE |
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