Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin, galectin-3.
Animal lectins play important roles in a variety of biological processes via their recognition of glycoconjugates. Galectin-3 is a beta-galactoside-binding lectin previously designated as epsilon BP (IgE-binding protein), CBP35, Mac-2, L-29, and L-34, and its expression has been associated with various physiological and pathological processes, including cell growth, tumor transformation, and metastasis. Galectin-3 is widely distributed in various tissues and cell types and is expressed in many leukocytes, with the notable exception of B and T lymphocytes. We now report that galectin-3 is abundantly expressed in a number of human T lymphotropic virus (HTLV)-I-infected human T cell lines, including F6T, HUT 102, K3T, MT-2, and SLB-I, but is not expressed in non-HTLV-I-infected T cell lines such as Jurkat, CEM, and MOLT-4. In addition, the galectin-3 level was markedly increased in human thymocytes after infection with HTLV-I as compared with uninfected thymocytes. The up-regulation of galectin-3 expression appeared to correlate well with HTLV-I gene expression, as undetectable or very low levels of galectin-3 were found in the S1T and ATL-1K cell lines, which are nonproductively infected with HTLV-I. In co-transfection experiments, the galectin-3 promoter was significantly up-regulated by expression vectors encoding the 40-kd Tax protein, a potent transactivator in HTLV-I. Analysis of various Tax mutants suggested that galectin-3 promoter induction is dependent on activation of the cyclic-AMP-responsive element binding protein/activation transcription factor family of transcription factors and, to a lesser extent, nuclear factor-kappa B/Rel induction. Transfection of human promonocytic U-937 cells with an HTLV-I Tax expression vector induced galectin-3 expression in this cell line. Functionally, galectin-3 was shown to activate interleukin-2 production in Jurkat T cells. Together, these findings raise the possibility that HTLV-I Tax production induces the transcription and subsequent synthesis and secretion of galectin-3, which in turn may further activate these T cells and contribute to the altered properties of cell growth found in adult T cell leukemia induced by HTLV-I.
Hsu
D K
DK
Scripps Research Institute, La Jolla, California 92037, USA.
Hammes
S R
SR
Kuwabara
I
I
Greene
W C
WC
Liu
F T
FT
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D037502:Galectin 3; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism; D005822:Genetic Vectors; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism* / Q000821:virology*; D013950:Thymus Gland / Q000737:chemistry / Q000166:cytology / Q000821:virology; D014162:Transfection
D000943:Antigens, Differentiation; D017362:Cyclic AMP Response Element-Binding Protein; D037502:Galectin 3; D016356:Gene Products, tax; D016328:NF-kappa B