In vitro spontaneous lymphoproliferation in patients with human T-cell lymphotropic virus type I-associated neurologic disease: predominant expansionof CD8+ T cells

Peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic p araparesis (HAM/TSP) proliferate spontaneously in vitro. This spontaneous l ymphoproliferation (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 ev aluated proliferating cell subsets in SP with a flow cytometric method usin g bromodeoxyuridine and Ki-67. Although both CD4(+) and CD8(+) T cells prol iferated spontaneously, the percentage of proliferating CW T cells was 2 to 5 times higher than that of CD4(+) T cells. In addition, more than 40% of HTLV-I Tax-11-19-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 findin g will help elucidate the dynamics of in vivo virus-host Immunologic intera ctions that permit the coexistence of high HTLV-I-specific, CD8+ cytotoxic T-lymphocyte responses and high HTLV-1 proviral load in HAM/TSP. (C) 2001 b y The American Society of Hematology.