Increased expression of human T lymphocyte virus type I (HTLV-I) Tax11-19 peptide-human histocompatibility leukocyte antigen A*201 complexes on CD4+ CD25+ T Cells detected by peptide-specific, major histocompatibility complex-restricted antibodies in patients with HTLV-I-associated neurologic disease.
J Exp Med
; 199(10): 1367-77, 2004 May 17.
Article
em En
| MEDLINE
| ID: mdl-15136590
ABSTRACT
Human T lymphocyte virus type I (HTLV-I)-associated chronic inflammatory neurological disease (HTLV-I-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) is suggested to be an immunopathologically mediated disorder characterized by large numbers of HTLV-I Tax-specific CD8+ T cells. The frequency of these cells in the peripheral blood and cerebrospinal fluid is proportional to the amount of HTLV-I proviral load and the levels of HTLV-I tax mRNA expression. As the stimulus for these virus-specific T cells are immunodominant peptide-human histocompatibility leukocyte antigen (HLA) complexes expressed on antigen-presenting cells, it was of interest to determine which cells express these complexes and at what frequency. However, until now, it has not been possible to identify and/or quantify these peptide-HLA complexes. Using a recently developed antibody that specifically recognizes Tax11-19 peptide-HLA-A*201 complexes, the level of Tax11-19-HLA-A*201 expression on T cells was demonstrated to be increased in HAM/TSP and correlated with HTLV-I proviral DNA load, HTLV-I tax mRNA load, and HTLV-I Tax-specific CD8+ T cell frequencies. Furthermore, CD4+ CD25+ T cells were demonstrated to be the major reservoir of HTLV-I provirus as well as Tax11-19 peptide-HLA-A*201 complexes. These results indicate that the increased detection and visualization of peptide-HLA complexes in HAM/TSP CD4+ CD25+ T cell subsets that are shown to stimulate and expand HTLV-I Tax-specific CD8+ T cells may play an important role in the pathogenesis of HTLV-I-associated neurological disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Antígenos HLA-A
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Vírus Linfotrópico T Tipo 1 Humano
/
Infecções por HTLV-I
/
Produtos do Gene tax
/
Doenças do Sistema Nervoso
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos