Virus and Autoantigen-Specific CD4+ T Cells Are Key Effectors in a SCID Mouse Model of EBV-Associated Post-Transplant Lymphoproliferative Disorders

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The γ-herpesvirus Epstein-Barr virus (EBV) is associated with several human malignancies, including post-transplant lymphoproliferative disorders (PTLD) in immunocompromised patients. The successful treatment of EBV-positive PTLD by the infusion of EBV-specific T-cell lines has provided an important proof of principle for immunotherapy of EBV-associated tumors and for cancer immunotherapy in general. EBV-specific T-cell preparations for clinical application are generated by repeated stimulation with autologous LCL in vitro. These lines contain CD4+ and CD8+ components but the specificity of the infused CD4+ T cells is still poorly defined. Using a mouse model of PTLD, we assessed the antitumoral potential of single virus-specific CD4+ T-cell clones. While T cells specific for a virion antigen of the virus prolonged mouse survival, other virus-specific clones had no effect or, unexpectedly, even promoted tumor growth. Moreover, the principal antitumoral effectors in LCL-stimulated T-cell preparations were CD4+ T cells specific for non-virus antigens. The definition of virion- and potentially autoantigen-specific CD4+ T cells as key effectors against PTLD may contribute to the design of generic and standardized protocols for the generation of T-cell lines with improved clinical efficacy. In addition, the observed tumor-promoting propensity of some CD4+ T cells may have implications for adoptive T-cell therapy in general.

Vyšlo v časopise: Virus and Autoantigen-Specific CD4+ T Cells Are Key Effectors in a SCID Mouse Model of EBV-Associated Post-Transplant Lymphoproliferative Disorders. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004068
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004068

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