Reflux of HTLV-I infected lymphocytes from the privileged compartment(s) to peripheral blood flow in patients with HTLV-I-associated myelopathy.

Abstract

To understand the mechanisms involved in the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), three in vivo phenomena which have been observed in the peripheral blood of patients and differing from that in asymptomatic HTLV-I carriers must be taken into consideration: (a) the presence of increased HTLV-I viral load, (b) a higher immune responsiveness against HTLV-I antigens, and (c) biased nucleotide substitutions in the HTLV-I pX region which indicate a decreased selection pressure for viral amino acid changes. We now propose a hypothesis which focuses on the in vivo dynamics of HTLV-I infected lymphocyte migration and which incorporates these features. In addition, the hypothesis assumes the existence of a deviation in immune surveillance for HTLV-I in the central nervous system (CNS) in spite of the presence of frequent specific immune effectors. We suggest that in the active phase of HAM/TSP, accompanied with or following autoaggressive interactions between infected lymphocytes and immunocompetent cells in the CNS, there is a consequential reflux of the infected lymphocytes to the peripheral blood. The reflux of infected cells would be expected to provide peripheral blood with tissue-derived HTLV-I proviruses which have been indulged and propagated in an immune-privileged site. This process would result in and account for the observed increase in viral load and the substitution bias in HTLV-I sequences in the peripheral blood.

• Authors: S Ijichi, N Ijichi, Y Yamano, W W Hall, M Osame
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 76 Issue 2 Pg. 117-25 (Feb 1998) ISSN: 0946-2716 [Print] Germany
• PMID: 9500677 (Publication Type: Journal Article)

Chemical References

• Deltaretrovirus Antibodies

Topics

• Deltaretrovirus Antibodies (blood, immunology)
• Human T-lymphotropic virus 1 (classification, genetics, immunology, physiology)
• Humans
• Leukocytes, Mononuclear (immunology)
• Lymphocytes (immunology)
• Models, Theoretical
• Mutation
• Paraparesis, Tropical Spastic (immunology)
• Proviruses
• Viral Load
• Virus Replication