CD44 splice variant involvement in the chronic inflammatory disease of the spinal cord: HAM/TSP.
Splice variants of CD44 molecule-harboring exon 10 (v6), often called v6 variants (v6v), are shown to confer tumor progressive, metastatic or invasive capacities. Furthermore, CD44 molecule on activated T-cells are shown to be required for infiltration of these cells into the inflammatory site and for accelerated immune response. Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is caused by HTLV-I infection and characterized by spastic paraparesis and urinary disturbance with perivascular HTLV-I-infected and activated CD4+ T-cell infiltration. In order to explore the underlying mechanism causing the disease after HTLV-I infection, we analyzed CD44 variant expression on peripheral blood mononuclear cells (PBMC) and in the spinal cord specimens from patients with HAM/TSP, and compared them with those from other HTLV-I-infected individuals and controls. We found that v6v expression with special direct link of exons 10 (v6) and 14(v10) was highly expressed in PBMC from patients with HAM/TSP and that v6v and CD4 double positive T-cell infiltration into the spinal cord lesion of HAM/TSP. This combination of CD44 splice variant has not been previously reported in the study of chronic inflammatory disorders and may be a marker molecule for T-cells infiltrating into the central nervous system (CNS), especially the spinal cord.
Matsuoka
E
E
Division of Molecular Pathology and Genetic Epidemiology, Center for Chronic Virus Diseases, Faculty of Medicine, Kagoshima University, Japan.
Usuku
K
K
Jonosono
M
M
Takenouchi
N
N
Izumo
S
S
Osame
M
M
D015139:Blotting, Southern; D002353:Carrier State; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D014644:Genetic Variation; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D015493:Paraparesis, Tropical Spastic / Q000235:genetics* / Q000276:immunology*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004274:DNA, Recombinant; D018960:Hyaluronan Receptors; D004247:DNA