HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis hypothesis. A shift of homologous peptides pairs, central nervous system (CNS)/HTLF-1, HTLV-1/thymus, thymus/CNS, in a thymus-like CNS environment, underlies the pathogenesis of HAM/TSP.
Determinants shared by thymus, brain and HTLV-1 induce lymphocytic neurotropism and demyelinization in HAM/TSP, within the framework thymus-like brain environment. The disease evolves in two phases. The first phase of the disease would be dependent on CD4 T-lymphocytes specific for thymic autoantigens, reactivated by viral antigens homologous to thymus and CNS autoantigens. During this phase, demyelinization could be due initially to a stop in the synthesis of myelin following an altered expression of adhesion proteins at the surface of oligodendrocytes and neurons. The second phase, which covers the inflammatory and chronic character of the disease, would be dependent, on the one hand, on CD8 T-lymphocytes specific for viral peptides, and on the other hand, on CD8 T-lymphocytes specific for peptides arising from the cell-proteases induced progressive proteolysis of protein components from the myelin layers and other protein components of the CNS. Non-specific inflammatory and non-inflammatory cytokines keep the activation going of the different cellular types. The thoracic spinal cord cell-location specificity would be linked to a peptidic coherence between HTLV-1 (significant agent), thymus and thoracic spinal cord antigens, genetically peculiar to HAM/TSP patients.
Plumelle
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Department of Hematobiology, University Hospital, Fort de France, Martinique, FWI. ffhemato@sasi.fr
D001921:Brain / Q000821:virology; D002465:Cell Movement; D003711:Demyelinating Diseases / Q000150:complications / Q000821:virology; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008954:Models, Biological; D018716:Molecular Mimicry; D015493:Paraparesis, Tropical Spastic / Q000209:etiology* / Q000821:virology; D012307:Risk Factors; D014764:Viral Proteins / Q000276:immunology
D014764:Viral Proteins