The Role of CTLs in Persistent Viral Infection: Cytolytic Gene Expression in CD8+ Lymphocytes Distinguishes between Individuals with a High or Low Proviral Load of Human T Cell Lymphotropic Virus Type 1
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- Alison M. Vine
- * Immunology and
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- Adrian G. Heaps
- * Immunology and
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- Lambrini Kaftantzi
- * Immunology and
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- Angelina Mosley
- * Immunology and
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- Becca Asquith
- * Immunology and
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- Aviva Witkover
- * Immunology and
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- Gillian Thompson
- * Immunology and
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- Mineki Saito
- * Immunology and
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- Peter K. C. Goon
- * Immunology and
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- Laura Carr
- ‡Johns Hopkins Medical Institute Microarray Core, Broadway Research Building, Johns Hopkins University, 733 North Broadway, Baltimore, MD 21205
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- Francisco Martinez-Murillo
- ‡Johns Hopkins Medical Institute Microarray Core, Broadway Research Building, Johns Hopkins University, 733 North Broadway, Baltimore, MD 21205
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- Graham P. Taylor
- †Infectious Diseases, Wright-Fleming Institute, Imperial College, Norfolk Place London United Kingdom; and
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- Charles R. M. Bangham
- * Immunology and
説明
<jats:title>Abstract</jats:title> <jats:p>The proviral load in human T cell lymphotropic virus type 1 (HTLV-1) infection is typically constant in each infected host, but varies by >1000-fold between hosts and is strongly correlated with the risk of HTLV-1-associated inflammatory disease. However, the factors that determine an individual’s HTLV-1 proviral load remain uncertain. Experimental evidence from studies of host genetics, viral genetics, and lymphocyte function and theoretical considerations suggest that a major determinant of the equilibrium proviral load is the CD8+ T cell response to HTLV-1. In this study, we tested the hypothesis that the gene expression profile in circulating CD8+ and CD4+ lymphocytes distinguishes between individuals with a low proviral load of HTLV-1 and those with a high proviral load. We show that circulating CD8+ lymphocytes from individuals with a low HTLV-1 proviral load overexpressed a core group of nine genes with strong functional coherence: eight of the nine genes encode granzymes or other proteins involved in cell-mediated lysis or Ag recognition. We conclude that successful suppression of the HTLV-1 proviral load is associated with strong cytotoxic CD8+ lymphocyte activity in the peripheral blood.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 173 (8), 5121-5129, 2004-10-15
The American Association of Immunologists