title: Modulation of interleukin-7 receptor expression characterizes differentiation of CD8 T cells specific for HIV, EBV and CMV.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratoire d'Immunologie Cellulaire, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Boutboul
authors.forename: Denis
authors.initials: D
authors.lastname: Puthier
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.forename: Olivier
authors.initials: O
authors.lastname: Pellé
authors.forename: Hocine
authors.initials: H
authors.lastname: Ait-Mohand
authors.forename: Béhazine
authors.initials: B
authors.lastname: Combadière
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Catherine
authors.initials: C
authors.lastname: Nguyen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008562:Membrane Glycoproteins / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D020395:Receptors, Interleukin-7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C415350:interleukin-7 receptor, alpha chain; D054353:Perforin