Abstract
Although natural killer (NK) cell-mediated control of viral infections is well documented, very little is known about the ability of NK cells to restrain human T-cell leukemia virus type 1 (HTLV-1) infection. In the current study we show that NK cells are unable to kill HTLV-1-infected primary CD4+ T cells. Exposure of NK cells to interleukin-2 (IL-2) resulted in only a marginal increase in their ability to kill HTLV-1-infected primary CD4+ T cells. This inability of NK cells to kill HTLV-1-infected CD4+ T cells occurred despite the down-modulation of major histocompatibility complex (MHC) class I molecules, one of the ligands for the major NK cell inhibitory receptor, by HTLV-1 p12(I) on CD4+ T cells. One reason for this diminished ability of NK cells to kill HTLV-1-infected cells was the decreased ability of NK cells to adhere to HTLV-1-infected cells because of HTLV-1 p12(I)-mediated down-modulation of intercellular adhesion molecule 1 (ICAM-1) and ICAM-2. We also found that HTLV-1-infected CD4+ T cells did not express ligands for NK cell activating receptors, NCR and NKG2D, although they did express ligands for NK cell coactivating receptors, NTB-A and 2B4. Thus, despite HTLV-1-mediated down-modulation of MHC-I molecules, HTLV-1-infected primary CD4+ T cells avoids NK cell destruction by modulating ICAM expression and shunning the expression of ligands for activating receptors.
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / immunology*
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / virology
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Cell Adhesion / drug effects
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Cell Adhesion / immunology
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Cell Adhesion Molecules / biosynthesis
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Cell Adhesion Molecules / immunology*
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Cell Line
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Coculture Techniques
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Down-Regulation / drug effects
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Down-Regulation / immunology*
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HTLV-I Infections / immunology*
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HTLV-I Infections / metabolism
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / immunology*
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Human T-lymphotropic virus 1 / immunology*
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Human T-lymphotropic virus 1 / metabolism
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Humans
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Immunity, Cellular / drug effects
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Intercellular Adhesion Molecule-1 / biosynthesis
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Intercellular Adhesion Molecule-1 / immunology*
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Interleukin-2 / pharmacology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Ligands
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / immunology
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NK Cell Lectin-Like Receptor Subfamily K
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Oncogene Proteins, Viral / immunology*
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Oncogene Proteins, Viral / metabolism
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Receptors, Cell Surface / biosynthesis
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Receptors, Cell Surface / immunology
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Receptors, Immunologic / biosynthesis
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Receptors, Immunologic / immunology
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Receptors, Natural Killer Cell
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Signaling Lymphocytic Activation Molecule Family
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Signaling Lymphocytic Activation Molecule Family Member 1
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Transcription Factors / immunology*
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Transcription Factors / metabolism
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Viral Regulatory and Accessory Proteins
Substances
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Antigens, CD
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CD244 protein, human
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Cell Adhesion Molecules
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Histocompatibility Antigens Class I
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ICAM2 protein, human
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IL2 protein, human
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Interleukin-2
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KLRK1 protein, human
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Ligands
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Membrane Glycoproteins
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NK Cell Lectin-Like Receptor Subfamily K
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Oncogene Proteins, Viral
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Receptors, Cell Surface
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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SLAMF6 protein, human
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Signaling Lymphocytic Activation Molecule Family
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Transcription Factors
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Viral Regulatory and Accessory Proteins
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p12I protein, Human T-lymphotropic virus 1
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Intercellular Adhesion Molecule-1
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Signaling Lymphocytic Activation Molecule Family Member 1