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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.
ISSN: 10985514
Appears in Collections:Scopus 2016-2017

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