No 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.

In a prospective study of 101 mother-child pairs in Jamaica, we examined the association of provirus load in breast milk and the risk of mother-to-child transmission of human T lymphotropic virus type I. The provirus load in breast milk was a strong predictor of risk of transmission to children (relative risk, 2.34/quartile), after adjustment for other known risk factors. The risk of transmission increased from 4.7/1000 personmonths when the provirus load in breast milk was !0.18% to 28.7/1000 person-months when it was 11.5%. Provirus detection in maternal breast milk predicted transmission months before infection in children was detected by serologic testing. Human T lymphotropic virus type I (HTLV-I) is etiologically associated with adult T cell leukemia/lymphoma (ATL), but!5% of HTLV-I-infected persons develop ATL [1]. Transmission of this virus occurs from mother to child [2,3], by sexual contact [4], or by the transfusion of cellular blood components [5,6]. Vertical transmission is an important route of transmission, because infection early in life is associated with a subsequent risk of ATL [7].Children born to HTLV-I-infected mothers acquire infection predominantly from breast-feeding [3,7]. A longer duration of breast-feeding has been associated with an increased risk of infection [3,8]. We have shown that the maternal HTLV-I provirus load in peripheral blood mononuclear cells (PBMCs)

No abstract

The worldwide geographic and ethnic clustering of patients with diseases related to human T-cell lymphotropic virus type I (HTLV-I) may be explained by the natural history of HTLV-I infection. The genetic characteristics of indigenous people in the Andes are similar to those of the Japanese, and HTLV-I is generally detected in both groups. To clarify the common origin of HTLV-I in Asia and the Andes, we analyzed HTLV-I provirus DNA from Andean mummies about 1,500 years old. Two of 104 mummy bone marrow specimens yielded a band of human beta-globin gene DNA 110 base pairs in length, and one of these two produced bands of HTLV-I-pX (open reading frame encoding p40x, p27x) and HTLV-I-LTR (long terminal repeat) gene DNA 159 base pairs and 157 base pairs in length, respectively. The nucleotide sequences of ancient HTLV-I-pX and HTLV-I-LTR clones isolated from mummy bone marrow were similar to those in contemporary Andeans and Japanese, although there was microheterogeneity in the sequences of some mummy DNA clones. This result provides evidence that HTLV-I was carried with ancient Mongoloids to the Andes before the Colonial era. Analysis of ancient HTLV-I sequences could be a useful tool for studying the history of human retroviral infection as well as human prehistoric migration.

Human T lymphotropic virus type I (HTLV-I) is endemic in southern Japan and the Caribbean, but the incidence of HTLV-I-associated diseases varies across geographic areas. We compared markers of disease pathogenesis among 51 age- and sex-matched HTLV-I carrier pairs from Japan and Jamaica. The mean antibody titer (P=.03) and detection of anti-Tax antibody (P=.002) were higher in Jamaican subjects than in Japanese subjects, but provirus load was similar between the 2 groups (P=.26). The correlation between antibody titer and provirus load was more prominent among Jamaican subjects than among Japanese subjects (P=.06). These findings underscore the differences in host immune response to HTLV-I infection in 2 populations.

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We found a significant dose-response relationship between HTLV-I transmission via breast-feeding and mother-child HLA class I type concordance. Immunological interactions between a child's cells and maternal cells may influence the risk of HTLV-I infection by breast-feeding, perhaps because antigens on maternal cells are seen by the child as being "self."