Induction of C chemokine XCL1 (lymphotactin/single C motif-1 alpha/activation-induced, T cell-derived and chemokine-related cytokine) expression by HIV-1 Tat protein

J Immunol. 2004 Feb 1;172(3):1888-95. doi: 10.4049/jimmunol.172.3.1888.

Abstract

HIV-1 Tat has been proposed as a key agent in many AIDS-related disorders, including HIV-1-associated neurological diseases. We have recently shown that Tat expression induces a significant increase in T lymphocytes in the brains of Tat transgenic mice. The CNS infiltration of T lymphocytes has been noted in AIDS patients. In the present study using this unique genetic system we attempted to understand the underlying mechanisms of Tat expression-induced infiltration of T lymphocytes by examining chemokine expression. RNase protection assay revealed that in addition to CCL2 (monocyte chemoattractant protein-1), CCL3 (macrophage inflammatory protein-1alpha (MIP-1alpha)), CCL4 (MIP-1beta), CCL5 (RANTES), CXCL2 (MIP-2), and CXCL10 (inducing protein-10), XCL1 (lymphotactin/single C motif-1alpha/activation-induced, T cell-derived and chemokine-related cytokine) was identified to be up-regulated by Tat expression. XCL1 is a C chemokine and plays a specific and important role in tissue-specific recruitment of T lymphocytes. Thus, we further determined the relationship between Tat and XCL1 expression. Tat-induced XCL1 expression was further confirmed by XCL1-specific RT-PCR and ELISA. Combined in situ hybridization and immunohistochemical staining identified astrocytes, monocytes, and macrophages/microglia as XCL1-producing cells in vivo. Using human astrocytes, U87.MG cells, as an in vitro model, activation of XCL1 expression was positively correlated with Tat expression. Moreover, the XCL1 promoter-driven reporter gene assay showed that Tat-induced XCL1 expression occurred at the transcriptional level. Taken together, these results demonstrate that Tat directly trans-activated XCL1 expression and suggest potential roles of Tat-induced XCL1 expression in the CNS infiltration of T lymphocytes during HIV-1 infection and subsequent HIV-1-induced neurological diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Brain / cytology
  • Brain / immunology
  • Brain / metabolism
  • Brain / virology
  • Cell Line, Tumor
  • Cells, Cultured
  • Chemokines, C / biosynthesis*
  • Chemokines, C / chemistry
  • Chemokines, C / genetics
  • Gene Expression Regulation
  • Gene Products, tat / biosynthesis
  • Gene Products, tat / genetics
  • Gene Products, tat / physiology*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Lymphocyte Activation
  • Lymphokines / chemistry
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Transgenic
  • Microglia / immunology
  • Microglia / metabolism
  • Monocytes / immunology
  • Monocytes / metabolism
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Sialoglycoproteins / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Up-Regulation / genetics
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Chemokines, C
  • Gene Products, tat
  • Lymphokines
  • RNA, Messenger
  • Sialoglycoproteins
  • XCL1 protein, human
  • Xcl1 protein, mouse
  • lymphotactin
  • tat Gene Products, Human Immunodeficiency Virus