caa a22 4500 467907501 CHVBK 20180406152839.0 cr unu---uuuuu 170328e20060501xx s 000 0 eng 10.1007/s00251-006-0082-9 doi (NATIONALLICENCE)springer-10.1007/s00251-006-0082-9 Immunostimulation by induced expression of NKG2D and its MIC ligands in HTLV-1-associated neurologic disease [Elektronische Daten] [Nazli Azimi, Steven Jacobson, Yuetsu Tanaka, Lawrence Corey, Veronika Groh, Thomas Spies] The NKG2D receptor costimulates effector/memory CD8 T cells and is normally absent on CD4 T cells but can be induced by T cell antigen receptor complex stimulation and interleukin-15 (IL-15). Among its ligands are the human major histocompatibility complex class I-related MICA and MICB, which have a restricted tissue distribution but are frequently associated with malignancies and some microbial infections. Moreover, aberrant expression of MIC may promote autoimmune disease progression. Human T cell lymphotropic virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system that resembles multiple sclerosis. Disease progression involves production of IL-15 and its receptor through transactivation by the viral Tax regulator protein, an activated immune response state, and local cytokine production and T cell fratricide by Tax-specific cytotoxic T lymphocytes (CTL). This study shows that as with CD8 T cells, substantial proportions of HAM/TSP patient CD4 T cells are positive for NKG2D and that large numbers of T cells from both subsets express MIC, which can be transactivated by Tax independent of nuclear factor κB. Engagement of MIC by NKG2D promotes spontaneous HAM/TSP T cell proliferation and, apparently, CTL activities against HTLV-1-infected T cells. These results reveal a viral strategy that may exploit immune stimulatory mechanisms to negotiate a balance between promotion and limitation of infected host T cell expansions. Springer-Verlag, 2006 NKG2D nationallicence MIC ligands nationallicence HTLV-1 nationallicence Tax nationallicence Transactivation nationallicence Azimi Nazli Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut Jacobson Steven Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 20892, Bethesda, MD, USA aut Tanaka Yuetsu Department of Infectious Disease and Immunology, Faculty of Medicine, Okinawa-Asia Research Center of Medical Science, University of the Ryukyus, 903-0215, Nishihara, Okinawa, Japan aut Corey Lawrence Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut Groh Veronika Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut Spies Thomas Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut Immunogenetics Springer-Verlag 58/4(2006-05-01), 252-258 0093-7711 58:4<252 2006 58 251 https://doi.org/10.1007/s00251-006-0082-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-006-0082-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Azimi Nazli Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut NATIONALLICENCE 700 1- Jacobson Steven Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Tanaka Yuetsu Department of Infectious Disease and Immunology, Faculty of Medicine, Okinawa-Asia Research Center of Medical Science, University of the Ryukyus, 903-0215, Nishihara, Okinawa, Japan aut NATIONALLICENCE 700 1- Corey Lawrence Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut NATIONALLICENCE 700 1- Groh Veronika Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut NATIONALLICENCE 700 1- Spies Thomas Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., 98109, Seattle, WA, USA aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 58/4(2006-05-01), 252-258 0093-7711 58:4<252 2006 58 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer