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Characterization of human CD8 T cell responses in dengue virus-infected patients from India
Chandele A. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Characterization of human CD8 T cell responses in dengue virus-infected patients from India
ผู้แต่ง / หัวหน้าโครงการ (EN): Chandele A.
บทคัดย่อ (EN): 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. © 2016, American Society for Microbiology. All Rights Reserved.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-85000995844&doi=10.1128%2fJVI.01424-16&partnerID=40&md5=73fe15dd62473194257370ed8dcd0288
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Viral Nonstructural Proteins
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Characterization of human CD8 T cell responses in dengue virus-infected patients from India
Chandele A.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
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