title: Increased expression of OX40 is associated with progressive disease in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.
abstract: BACKGROUND
  OX40 is a member of the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells and promotes the development of effector and memory T cells. Although OX40 has been reported to be a target gene of human T-cell leukemia virus type-1 (HTLV-1) viral transactivator Tax and is overexpressed in vivo in adult T-cell leukemia (ATL) cells, an association between OX40 and HTLV-1-associated inflammatory disorders, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), has not yet been established. Moreover, because abrogation of OX40 signals ameliorates chronic inflammation in animal models of autoimmune disease, novel monoclonal antibodies against OX40 may offer a potential treatment for HTLV-1-associated diseases such as ATL and HAM/TSP.
  
  
  RESULTS
  In this study, we showed that OX40 was specifically expressed in CD4+ T cells naturally infected with HTLV-1 that have the potential to produce pro-inflammatory cytokines along with Tax expression. We also showed that OX40 was overexpressed in spinal cord infiltrating mononuclear cells in a clinically progressive HAM/TSP patient with a short duration of illness. The levels of the soluble form of OX40 (sOX40) in the cerebrospinal fluid (CSF) from chronic progressive HAM/TSP patients or from patients with other inflammatory neurological diseases (OINDs) were not different. In contrast, sOX40 levels in the CSF of rapidly progressing HAM/TSP patients were higher than those in the CSF from patients with OINDs, and these patients showed higher sOX40 levels in the CSF than in the plasma. When our newly produced monoclonal antibody against OX40 was added to peripheral blood mononuclear cells in culture, HTLV-1-infected T cells were specifically removed by a mechanism that depends on antibody-dependent cellular cytotoxicity.
  
  
  CONCLUSIONS
  Our study identified OX40 as a key molecule and biomarker for rapid progression of HAM/TSP. Furthermore, blocking OX40 may have potential in therapeutic intervention for HAM/TSP.
authors: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Okinawa, Japan. mineki@med.kawasaki-m.ac.jp
authors: Mineki
authors: M
authors: Saito
authors: Reiko
authors: R
authors: Tanaka
authors: Shiho
authors: S
authors: Arishima
authors: Toshio
authors: T
authors: Matsuzaki
authors: Satoshi
authors: S
authors: Ishihara
authors: Takashi
authors: T
authors: Tokashiki
authors: Yusuke
authors: Y
authors: Ohya
authors: Hiroshi
authors: H
authors: Takashima
authors: Fujio
authors: F
authors: Umehara
authors: Shuji
authors: S
authors: Izumo
authors: Yuetsu
authors: Y
authors: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000473:pathology*; D053262:Receptors, OX40 / Q000032:analysis*
chemical_list: D015415:Biomarkers; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human
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