Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease.
HTLV-1 is the etiologic agent of a debilitating neurologic disorder, HAM/TSP. This disease features a robust immune response including the oligoclonal expansion of CD8+ CTLs specific for the viral oncoprotein Tax. The key pathogenic process resulting in the proliferation of CTLs and the presentation of Tax peptide remains uncharacterized. We have investigated the role of APCs, particularly DCs, in priming of the anti-Tax CTL response under in vitro and in vivo conditions. We investigated two routes (direct vs. indirect) of Tax presentation using live virus, infected primary CD4+/CD25+ T cells, and the CD4+ T cell line (C8166, a HTLV-1-mutated line that only expresses Tax). Our results indicated that DCs are capable of priming a pronounced Tax-specific CTL response in cell cultures consisting of naïve PBLs as well as in HLA-A*0201 transgenic mice (line HHD II). DCs were able to direct the presentation of Tax successfully through infected T cells, live virus, and cell-free Tax. These observations were comparable with those made with a known stimulant of DC maturation, a combination of CD40L and IFN-gamma. Our studies clearly establish a role for this important immune cell component in HTLV-1 immuno/neuropathogenesis and suggest that modulation of DC functions could be an important tool for therapeutic interventions.
Manuel
Sharrón L
SL
Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Schell
Todd D
TD
Acheampong
Edward
E
Rahman
Saifur
S
Khan
Zafar K
ZK
Jain
Pooja
P
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D006800:Deltaretrovirus Infections / Q000276:immunology / Q000503:physiopathology*; D003713:Dendritic Cells / Q000276:immunology*; D016356:Gene Products, tax / Q000096:biosynthesis* / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D009422:Nervous System Diseases / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology
D015703:Antigens, CD; D016356:Gene Products, tax; D053645:Interleukin-2 Receptor alpha Subunit; C514970:tax protein, Human T-lymphotrophic virus 1; D007371:Interferon-gamma