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Title: | Characterization of human CD8 T cell responses in dengue virus-infected patients from India |
Authors: | Anmol Chandele Jaturong Sewatanon Sivaram Gunisetty Mohit Singla Nattawat Onlamoon Rama S. Akondy Haydn Thomas Kissick Kaustuv Nayak Elluri Seetharami Reddy Haroon Kalam Dhiraj Kumar Anil Verma Hare Krushna Panda Siyu Wang Nasikarn Angkasekwinai Kovit Pattanapanyasat Kulkanya Chokephaibulkit Guruprasad R. Medigeshi Rakesh Lodha Sushil Kabra Rafi Ahmed Kaja Murali-Krishna International Centre for Genetic Engineering and Biotechnology, New Delhi All India Institute of Medical Sciences, New Delhi Mahidol University Emory University School of Medicine Translational Health Science and Technology Institute |
Keywords: | Agricultural and Biological Sciences;Immunology and Microbiology |
Issue Date: | 1-Jan-2016 |
Citation: | Journal of Virology. Vol.90, No.24 (2016), 11259-11278 |
Abstract: | © 2016, American Society for Microbiology. All Rights Reserved. Epidemiological studies suggest that India has the largest number of dengue virus infection cases worldwide. However, there is minimal information about the immunological responses in these patients. CD8 T cells are important in dengue, because they have been implicated in both protection and immunopathology. Here, we provide a detailed analysis of HLA-DR- CD38+ and HLA-DR+ CD38+ effector CD8 T cell subsets in dengue patients from India and Thailand. Both CD8 T cell subsets expanded and expressed markers indicative of antigen-driven proliferation, tissue homing, and cytotoxic effector functions, with the HLADR+ CD38+ subset being the most striking in these effector qualities. The breadth of the dengue-specific CD8 T cell response was diverse, with NS3-specific cells being the most dominant. Interestingly, only a small fraction of these activated effector CD8 T cells produced gamma interferon (IFN-γ) when stimulated with dengue virus peptide pools. Transcriptomics revealed downregulation of key molecules involved in T cell receptor (TCR) signaling. Consistent with this, the majority of these CD8 T cells remained IFN-γ unresponsive even after TCR-dependent polyclonal stimulation (anti-CD3 plus anti-CD28) but produced IFN-γ by TCR-independent polyclonal stimulation (phorbol 12-myristate 13-acetate [PMA] plus ionomycin). Thus, the vast majority of these proliferating, highly differentiated effector CD8 T cells probably acquire TCR refractoriness at the time the patient is experiencing febrile illness that leads to IFN-γ unresponsiveness. Our studies open novel avenues for understanding the mechanisms that fine-tune the balance between CD8 T cell-mediated protective versus pathological effects in dengue. |
URI: | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85000995844&origin=inward http://repository.li.mahidol.ac.th/dspace/handle/123456789/42848 |
ISSN: | 10985514 0022538X |
Appears in Collections: | Scopus 2016-2017 |
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