title: Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells.
abstract: Most human T cell leukemia virus type 1 (HTLV-1) infected subjects remain asymptomatic throughout their lives, with a few individuals developing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia. Lymphocytes from about half of HTLV-1 infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease outcome and viral burden is poorly understood. Spontaneous proliferation was measured in lymphocyte subsets, and these findings were correlated with HTLV-1 proviral load and Tax expression in PBMCs. We found that in addition to previously described vigorous CD8+ T cell spontaneous proliferation, natural killer (NK) cells spontaneously proliferated to a similar high level, resulting in expansion of CD56-expressing NK cells. Spontaneous NK cell proliferation positively correlated with HTLV-1 proviral load but not with Tax expression or the presence of HAM/TSP. The strongest correlate with clinical outcome in this cohort was the ability of cells to express Tax, while HTLV-1 proviral load was more closely related to spontaneous NK cell proliferation. These results demonstrate that spontaneous proliferation, Tax expression, and proviral load are inter-related but not equivalent, and that spontaneous lymphocyte proliferation is not restricted to T cells, the targets of HTLV-1 infection.
authors.affiliation: Blood Systems Research Institute, and Department of Laboratory Medicine, University of California, San Francisco, CA, USA. pnorris@bloodsystems.org
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: Dale F
authors.initials: DF
authors.lastname: Hirschkorn
authors.forename: Deborah A
authors.initials: DA
authors.lastname: DeVita
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Edward L
authors.initials: EL
authors.lastname: Murphy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D016356:Gene Products, tax / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D055815:Young Adult
chemical_list: D019002:CD56 Antigen; D016356:Gene Products, tax; C522918:NCAM1 protein, human; C514970:tax protein, Human T-lymphotrophic virus 1