Virus-specific T lymphocytes home to the skin during natural dengue infection

Laura Rivino, et al. 2015. Sci Transl Med 7, 278ra35

Speaker: Wan-Yu Wang (王琬瑜)                                 Time: 14:00~15:00, Dec. 02, 2015

Commentator: Guey-Chuen Perng (彭貴春 老師)     Place: Room 601

Abstract

        Dengue disease has spread widely through the world, mainly occurs in tropical and subtropical areas. Dengue virus is transmitted around people via the mosquitoes, and usually results in fever, skin rash, joint/muscle pain, and even bleeding. During dengue infection, viral antigens are presented by local antigen presenting cells (APCs), and induce a broad T cell response. However, the role and function of virus-specific T cells during acute dengue infection are still not fully understood. The viral nonstructural proteins NS3 and NS5 are major stimulus to T cell response (1). In this study, the authors detected dengue-specific CD8⁺ T cells from patient peripheral blood mononuclear cells (PBMCs) by HLA class I pentamers (HLA-A*1101–restricted NS3 27 peptide) (2), and found that DENV-specific CD8⁺ T cells showed activation, proliferation and antiviral activity during acute dengue infection. Furthermore, the authors observed the increased expression of skin homing markers including cutaneous lymphocyte-associated antigen (CLA) and chemokine receptors CXCR3/CCR5 on T cells for its homing to peripheral tissues during inflammation. In addition, T cells which carry immunological memory were also determined by markers including CCR7 and CD45RA. However, other activated T cells specific to HCMV pentamers were unable to express CLA. It indicated that the skin homing ability of T cells is specific to dengue infection. To investigate whether the skin-homing phenotype was also induced by other dengue epitopes, the NS3/NS5 mixture was capable of activating both CD4⁺ and CD8⁺ T cells to express skin-homing markers. From clinical isolation of skin blister fluid, dengue-specific T cells were significantly enriched in dengue infection. In conclusion, the local enrichment of DENV-specific T cells plays an important role in immediate and subsequent dengue infections. The discovery of skin-homing T cells may have important implications for dengue vaccine design.

Reference:

1.         L. Rivino, et al, Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue infection. 2013. J. Virol. 87, 2693–2706.

2.         J. Mongkolsapaya, et al, Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. 2003. Nat. Med. 9, 921–927.