How does interleukin 15 contribute to the pathogenesis of HTLV type 1-associated myelopathy/tropical spastic paraparesis?
HTLV-1 is the etiological agent of a neurological disease named HAM/TSP that has clinical characteristics similar to those of multiple sclerosis (MS). The PBMC obtained from HAM/TSP patients undergo spontaneous proliferation in the absence of addition of any exogenous cytokines in an ex vivo culture. This spontaneous proliferation has been thought to be due to the proliferation of T cells. It was demonstrated that this proliferation is, in part, due to the production of IL-2 and its receptor (IL-2Ralpha) by HTLV-1-infected T cells. In this review, we demonstrate that IL-15 production also contributes to the spontaneous proliferation of T cells obtained from HAM/TSP PBMC. We provide data indicating that IL-15 expression is elevated in HAM/TSP PBMC when compared to that of the normal donors. Furthermore, we demonstrate that IL-15 overexpression by HTLV-1 is due to Tax trans-activation of its promoter and induction of NF-kappaB transcription factors. On the basis of these studies, we propose a model in which HTLV-1 infection of T cells results in the production of both IL-2 and IL-15 cytokines, growth factors that support the proliferation of T cells.
Azimi
N
N
Metabolism Branch, National Cancer Institutes, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. nazli@helix.nih.gov
Mariner
J
J
Jacobson
S
S
Waldmann
T A
TA
D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000821:virology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
D016356:Gene Products, tax; D019409:Interleukin-15; D012333:RNA, Messenger