Human parainfluenza virus-3 can be targeted by rapidly ex vivo expanded T lymphocytes
| Autor: | Conrad Russell Y. Cruz, Haili Lang, Lauren P. McLaughlin, Anamaris M. Colberg-Poley, Patrick J. Hanley, Catherine M. Bollard, Kaylor E. Wright, Michael D. Keller, Elizabeth Williams, Cecilia Barese, Allison B. Powell |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Cancer Research Immunology CD4-CD8 Ratio Cell- and Tissue-Based Therapy Biology CD8-Positive T-Lymphocytes Respirovirus Infections Article Immunophenotyping 03 medical and health sciences Interleukin 21 Immunocompromised Host Interferon-gamma Antigen Immunology and Allergy Cytotoxic T cell Humans Lymphocyte Count Antigen-presenting cell Antigens Viral Genetics (clinical) Cells Cultured Transplantation ELISPOT Cell Biology Natural killer T cell Flow Cytometry Virology Parainfluenza Virus 3 Human 030104 developmental biology Oncology Interleukin 12 CD8 |
| Zdroj: | Cytotherapy. 18(12) |
| ISSN: | 1477-2566 |
| Popis: | Background aims Human parainfluenza virus-3 (HPIV) is a common cause of respiratory infection in immunocompromised patients and currently has no effective therapies. Virus-specific T-cell therapy has been successful for the treatment or prevention of viral infections in immunocompromised patients but requires determination of T-cell antigens on targeted viruses. Methods HPIV3-specific T cells were expanded from peripheral blood of healthy donors using a rapid generation protocol targeting four HPIV3 proteins. Immunophenotyping was performed by flow cytometry. Viral specificity was determined by interferon (IFN)-γ ELISpot, intracellular cytokine staining and cytokine measurements from culture supernatants by Luminex assay. Cytotoxic activity was tested by 51 Cr release and CD107a mobilization assays. Virus-specific T cells targeting six viruses were then produced by rapid protocol, and the phenotype of HPIV3-specific T cells was determined by immunomagnetic sorting for IFN-γ-producing cells. Results HPIV3-specific T cells were expanded from 13 healthy donors. HPIV3-specific T cells showed a CD4 + predominance (mean CD4:CD8 ratio 2.89) and demonstrated specificity for multiple HPIV3 antigens. The expanded T cells were polyfunctional based on cytokine production but only had a minor cytotoxic component. T cells targeting six viruses in a single product similarly showed HPIV3 specificity, with a predominant effector memory phenotype (CD3 + /CD45RA – /CCR7 – ) in responder cells. Discussion HPIV3-specific T cells can be produced using a rapid ex vivo protocol from healthy donors and are predominantly CD4 + T cells with Th1 activity. HPIV3 epitopes can also be successfully targeted alongside multiple other viral epitopes in production of six-virus T cells, without loss of HPIV3 specificity. These products may be clinically beneficial to combat HPIV3 infections by adoptive T-cell therapy in immune-compromised patients. |
| Databáze: | OpenAIRE |
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