- Meeting abstract
- Open Access
Neural bystander damage by infiltrating virus-infected T cells and the cytotoxic T lymphocytes in HTLV-I-associated neurological disease
© Matsuura et al; licensee BioMed Central Ltd. 2011
- Published: 6 June 2011
- Spinal Cord
- Apoptotic Cell
- Cerebrospinal Fluid
- Neurological Disease
We hypothesized that the cytotoxic T lymphocytes(CTLs) play a pivotal role in the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spasticparaparesis(HAM/TSP).
One of the most striking features of the cellular immune response in the patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the highly increased numbers of HTLV-I-specific cytotoxic T lymphocytes (CTLs) in the circulation of the blood and the cerebrospinal fluid, nevertheless HTLV-I proviral load in the PBMC remains high in the patients.
To determine the CTL’s association with the pathogenesis of HAM/TSP in the CNS, we developed novel methods of in-situ detection for HTLV-I-specific CTL using HLA/antigen peptide tetramer and for the cells expressing HTLV-I viral protein. We visualized the HTLV-I specific CTLs and HTLV-I-infected cells in autopsied spinal cords of the patients with HAM/TSP.
We demonstrated that HTLV-I-specific CTLs expressing cytotoxic molecules accumulated in the spinal cords from three patients with HAM/TSP and that HTLV-I exclusively infected CD4 positive T lymphocytes but neither resident cells nor macrophages. The phenotype of apoptotic cells was HTLV-I infected CD4+ T lymphocytes or HTLV-I non-infected oligodendrocytes.
The findings suggest a unique pathogenesis for the neuroinflammatory disease that an inflammation of the central nervous system is attributed to the interaction between HTLV-I-infected CD4+ T cells and HTLV-I-specific CD8+ CTLs from the periphery.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.