Modulation of interleukin-7 receptor expression characterizes differentiation of CD8 T cells specific for HIV, EBV and CMV

To further understand differentiation and homeostasis of CD8 T cells specific for HIV, Epstein-Barr Virus (EBV) and cytomegalovirus (CMV) during HIV infection, we investigated interleukin-7 receptor alpha (IL-7Ralpha) expression on those virus-specific T cells. Microarrays and cytometry analyses wer...

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Veröffentlicht in:AIDS (London) 2005-11, Vol.19 (17), p.1981-1986
Hauptverfasser: BOUTBOUL, Francois, PUTHIER, Denis, NGUYEN, Catherine, AUTRAN, Brigitte, APPAY, Victor, PELLE, Olivier, AIT-MOHAND, Hocine, COMBADIERE, Béhazine, CARCELAIN, Ghislaine, KATLAMA, Christine, ROWLAND-JONES, Sarah L, DEBRE, Patrice
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container_end_page 1986
container_issue 17
container_start_page 1981
container_title AIDS (London)
container_volume 19
creator BOUTBOUL, Francois
PUTHIER, Denis
NGUYEN, Catherine
AUTRAN, Brigitte
APPAY, Victor
PELLE, Olivier
AIT-MOHAND, Hocine
COMBADIERE, Béhazine
CARCELAIN, Ghislaine
KATLAMA, Christine
ROWLAND-JONES, Sarah L
DEBRE, Patrice
description To further understand differentiation and homeostasis of CD8 T cells specific for HIV, Epstein-Barr Virus (EBV) and cytomegalovirus (CMV) during HIV infection, we investigated interleukin-7 receptor alpha (IL-7Ralpha) expression on those virus-specific T cells. Microarrays and cytometry analyses were performed on peripheral blood mononuclear cells (PBMC), total and tetramer-binding virus-specific CD8 T cells from 66 HIV-infected patients. Microarray analysis revealed reduced levels of IL-7Ralpha and increased levels of perforin with disease progression in total PBMC. This loss of IL-7Ralpha expression was observed on CD8 T cells and was inversely related to perforin expression. The relative expression of both molecules defined three new subsets: IL-7Ralpha(pos)Perforin(neg); IL-7Ralpha(loneg)Perforin(lo); and IL-7Ralpha(loneg)Perforin(hi) corresponding to naive and effector-memory CD8 differentiation, as assessed by CD45RA/CD11a. The IL-7Ralpha expression decreased along the CD8 differentiation pathway defined by CD27 and CD28. In contrast, IL-7Ralpha expression was down-modulated on all the CD8 T cells specific for HIV, EBV and CMV that were almost exclusively IL-7Ralpha(lo/neg)Perforin(lo) and was parallel with the CD27 expression. In addition, this low IL-7Ralpha expression on HIV-specific CD8 T cells was independent of virus load and T-cell activation and remained stable during the first 6 months of antiretroviral therapy despite successful control of HIV replication. The relative expression of IL-7Ralpha, perforin reveals new aspects of virus-specific CD8 T cell differentiation, independently of T-cell activation and virus load. This opens new perspectives for understanding homeostasis of those cells and immune-based therapeutic strategies.
doi_str_mv 10.1097/01.aids.0000191919.24185.46
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Microarrays and cytometry analyses were performed on peripheral blood mononuclear cells (PBMC), total and tetramer-binding virus-specific CD8 T cells from 66 HIV-infected patients. Microarray analysis revealed reduced levels of IL-7Ralpha and increased levels of perforin with disease progression in total PBMC. This loss of IL-7Ralpha expression was observed on CD8 T cells and was inversely related to perforin expression. The relative expression of both molecules defined three new subsets: IL-7Ralpha(pos)Perforin(neg); IL-7Ralpha(loneg)Perforin(lo); and IL-7Ralpha(loneg)Perforin(hi) corresponding to naive and effector-memory CD8 differentiation, as assessed by CD45RA/CD11a. The IL-7Ralpha expression decreased along the CD8 differentiation pathway defined by CD27 and CD28. In contrast, IL-7Ralpha expression was down-modulated on all the CD8 T cells specific for HIV, EBV and CMV that were almost exclusively IL-7Ralpha(lo/neg)Perforin(lo) and was parallel with the CD27 expression. In addition, this low IL-7Ralpha expression on HIV-specific CD8 T cells was independent of virus load and T-cell activation and remained stable during the first 6 months of antiretroviral therapy despite successful control of HIV replication. The relative expression of IL-7Ralpha, perforin reveals new aspects of virus-specific CD8 T cell differentiation, independently of T-cell activation and virus load. 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Psychology ; Gene Expression - genetics ; HIV Infections - genetics ; HIV Infections - immunology ; HIV-1 - genetics ; HIV-1 - immunology ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Leukocytes, Mononuclear - immunology ; Medical sciences ; Membrane Glycoproteins - analysis ; Molecular and cellular biology ; Oligonucleotide Array Sequence Analysis - methods ; Perforin ; Pore Forming Cytotoxic Proteins ; Receptors, Interleukin-7 - immunology ; Transcription, Genetic - genetics ; Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics ; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. 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Microarrays and cytometry analyses were performed on peripheral blood mononuclear cells (PBMC), total and tetramer-binding virus-specific CD8 T cells from 66 HIV-infected patients. Microarray analysis revealed reduced levels of IL-7Ralpha and increased levels of perforin with disease progression in total PBMC. This loss of IL-7Ralpha expression was observed on CD8 T cells and was inversely related to perforin expression. The relative expression of both molecules defined three new subsets: IL-7Ralpha(pos)Perforin(neg); IL-7Ralpha(loneg)Perforin(lo); and IL-7Ralpha(loneg)Perforin(hi) corresponding to naive and effector-memory CD8 differentiation, as assessed by CD45RA/CD11a. The IL-7Ralpha expression decreased along the CD8 differentiation pathway defined by CD27 and CD28. In contrast, IL-7Ralpha expression was down-modulated on all the CD8 T cells specific for HIV, EBV and CMV that were almost exclusively IL-7Ralpha(lo/neg)Perforin(lo) and was parallel with the CD27 expression. In addition, this low IL-7Ralpha expression on HIV-specific CD8 T cells was independent of virus load and T-cell activation and remained stable during the first 6 months of antiretroviral therapy despite successful control of HIV replication. The relative expression of IL-7Ralpha, perforin reveals new aspects of virus-specific CD8 T cell differentiation, independently of T-cell activation and virus load. This opens new perspectives for understanding homeostasis of those cells and immune-based therapeutic strategies.</description><subject>AIDS/HIV</subject><subject>Antiretroviral Therapy, Highly Active - methods</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>CD28 Antigens - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Differentiation - immunology</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cells, Cultured</subject><subject>Computer Science</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus Infections - genetics</subject><subject>Cytomegalovirus Infections - immunology</subject><subject>Epstein-Barr virus</subject><subject>Epstein-Barr Virus Infections - genetics</subject><subject>Epstein-Barr Virus Infections - immunology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - genetics</subject><subject>HIV Infections - genetics</subject><subject>HIV Infections - immunology</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - analysis</subject><subject>Molecular and cellular biology</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Perforin</subject><subject>Pore Forming Cytotoxic Proteins</subject><subject>Receptors, Interleukin-7 - immunology</subject><subject>Transcription, Genetic - genetics</subject><subject>Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics</subject><subject>Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. 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Psychology</topic><topic>Gene Expression - genetics</topic><topic>HIV Infections - genetics</topic><topic>HIV Infections - immunology</topic><topic>HIV-1 - genetics</topic><topic>HIV-1 - immunology</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - analysis</topic><topic>Molecular and cellular biology</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Perforin</topic><topic>Pore Forming Cytotoxic Proteins</topic><topic>Receptors, Interleukin-7 - immunology</topic><topic>Transcription, Genetic - genetics</topic><topic>Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics</topic><topic>Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. 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subjects AIDS/HIV
Antiretroviral Therapy, Highly Active - methods
Bioinformatics
Biological and medical sciences
CD28 Antigens - immunology
CD8-Positive T-Lymphocytes - immunology
Cell Differentiation - immunology
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
Cells, Cultured
Computer Science
Cytomegalovirus
Cytomegalovirus Infections - genetics
Cytomegalovirus Infections - immunology
Epstein-Barr virus
Epstein-Barr Virus Infections - genetics
Epstein-Barr Virus Infections - immunology
Fundamental and applied biological sciences. Psychology
Gene Expression - genetics
HIV Infections - genetics
HIV Infections - immunology
HIV-1 - genetics
HIV-1 - immunology
Human immunodeficiency virus
Human viral diseases
Humans
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunopathology
Infectious diseases
Leukocytes, Mononuclear - immunology
Medical sciences
Membrane Glycoproteins - analysis
Molecular and cellular biology
Oligonucleotide Array Sequence Analysis - methods
Perforin
Pore Forming Cytotoxic Proteins
Receptors, Interleukin-7 - immunology
Transcription, Genetic - genetics
Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics
Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
title Modulation of interleukin-7 receptor expression characterizes differentiation of CD8 T cells specific for HIV, EBV and CMV
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