Publication: Characterization of human CD8 T cell responses in dengue virus-infected patients from India
Issued Date
2016-01-01
Resource Type
ISSN
10985514
0022538X
0022538X
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2-s2.0-85000995844
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Virology. Vol.90, No.24 (2016), 11259-11278
Suggested Citation
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 Characterization of human CD8 T cell responses in dengue virus-infected patients from India. Journal of Virology. Vol.90, No.24 (2016), 11259-11278. doi:10.1128/JVI.01424-16 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42848
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Title
Characterization of human CD8 T cell responses in dengue virus-infected patients from India
Author(s)
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
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
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.