In vitro spontaneous lymphoproliferation in patients with human T-cell lymphotropic virus type I-associated neurologic disease: predominant expansion of CD8+ T cells.
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.
Sakai
J A
JA
Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Nagai
M
M
Brennan
M B
MB
Mora
C A
CA
Jacobson
S
S
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002455:Cell Division; D002478:Cells, Cultured; D004261:DNA Replication; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D016356:Gene Products, tax / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000150:complications*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification
D004279:DNA, Viral; D016356:Gene Products, tax; D006680:HLA Antigens