Human T-cell leukemia virus type 1 (HTLV-1) p12I down-modulates ICAM-1 and -2 and reduces adherence of natural killer cells, thereby protecting HTLV-1-infected primary CD4+ T cells from autologous natural killer cell-mediated cytotoxicity despite the reduction of major histocompatibility complex class I molecules on infected cells.
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.
Banerjee
Prabal
P
Department of Immunology and Microbiology, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA.
Feuer
Gerold
G
Barker
Edward
E
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology*; D002460:Cell Line; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D015490:HTLV-I Infections / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009856:Oncogene Proteins, Viral / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
D015703:Antigens, CD; C084093:CD244 protein, human; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; C065289:ICAM2 protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; C527085:KLRK1 protein, human; D008024:Ligands; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009856:Oncogene Proteins, Viral; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C000604060:SLAMF6 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C084305:p12I protein, Human T-lymphotropic virus 1; D018799:Intercellular Adhesion Molecule-1; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1