ABSTRACT
It is thought that human T-cell lymphotropic virus type I (HTLV-I) preferentially infects CD4(+) T cells in vivo. However, observations of high HTLV-I proviral load in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis suggest that HTLV-I may infect other cell types in addition to CD4(+) T cells. To identify in vivo T-cell tropisms of HTLV-I, real-time quantitative polymerase chain reaction (PCR) and intracellular protein staining were used. A high amount of HTLV-I proviral DNA was detected from purified CD8(+) T cells by quantitative PCR (between 1.64 and 62.83 copies of HTLV-I provirus per 100 isolated CD8(+) T cells). CD8(+) T cells expressed HTLV-I-related antigens (HTLV-I Tax and p19 protein) after a short time in cultivation. These results demonstrate that CD8(+) T cells are also infected with HTLV-I and express HTLV-I antigens at levels that are comparable to HTLV-I-infected CD4(+) cells. Therefore, CD8(+) cells are an additional viral reservoir in vivo for HTLV-I and may contribute to the pathogenesis of HTLV-I-mediated disorders.
Subject(s)
CD8-Positive T-Lymphocytes/virology , Human T-lymphotropic virus 1/isolation & purification , CD4-Positive T-Lymphocytes/virology , Cells, Cultured , DNA, Viral/analysis , Gene Products, gag/metabolism , Gene Products, tax/metabolism , Human T-lymphotropic virus 1/genetics , Humans , Retroviridae Proteins, Oncogenic/metabolism , gag Gene Products, Human Immunodeficiency VirusABSTRACT
Peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) proliferate spontaneously in vitro. This spontaneous lymphoproliferation (SP) is one of the immunologic hallmarks of HAM/TSP and is considered to be an important factor related to the pathogenesis of HAM/TSP. However, the cell populations involved in this phenomenon have not yet been definitively identified. To address this issue, the study directly evaluated proliferating cell subsets in SP with a flow cytometric method using bromodeoxyuridine and Ki-67. Although both CD4+ and CD8+ T cells proliferated spontaneously, the percentage of proliferating CD8+ T cells was 2 to 5 times higher than that of CD4+ T cells. In addition, more than 40% of HTLV-I Tax11-19-specific CD8+ T cells as detected by an HLA-A*0201/Tax11-19 tetramer proliferated in culture. In spite of this expansion of HTLV-I-specific CD8+ T cells, HTLV-I proviral load did not decrease. This finding will help elucidate the dynamics of in vivo virus-host immunologic interactions that permit the coexistence of high HTLV-I-specific CD8+ cytotoxic T-lymphocyte responses and high HTLV-I proviral load in HAM/TSP.
