title: Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency.
abstract: BACKGROUND
  A subset of patients with common variable immunodeficiency (CVID) have debilitating inflammatory complications strongly associated with cytomegalovirus (CMV) infection and a hyperproliferative CMV-specific T-cell response.
  
  
  OBJECTIVE
  We studied the T-cell response to CMV and the global effect of this virus on immune effector cell populations in patients with CVID.
  
  
  METHODS
  Antibody staining, peptide stimulation, and proliferation assays were used to profile CMV-specific T-cell function.
  
  
  RESULTS
  CMV infection drives the CD4/CD8 ratio inversion that is characteristic of CVID. The late effector CD8(+) T-cell subset is expanded in CMV-infected patients with CVID. This expansion is largely attributable to CMV-specific cells and correlates with inflammatory disease; within the CMV-specific population, the frequency of late effector cells correlates inversely with the frequency of cells expressing programmed death 1. Supernatants from proliferating CMV-specific CD8(+) cells from patients with inflammatory disease can confer proliferative potential on cells from patients with noninflammatory CVID and healthy subjects. Blocking experiments showed that this proliferation is mediated in part by IFN-γ and TNF-α.
  
  
  CONCLUSIONS
  These data strengthen the association of CMV with inflammatory pathology in patients with CVID, explain some of the well-known T-cell abnormalities associated with this condition, and provide a plausible mechanism for the documented therapeutic activity of anti-TNF-α and antiviral chemotherapy in managing CVID-associated inflammatory disease.
authors.affiliation: Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, Royal Free Campus, University College London Medical School, London, United Kingdom.
authors.forename: Sayed Mahdi
authors.initials: SM
authors.lastname: Marashi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Raeiszadeh
authors.forename: Victoria
authors.initials: V
authors.lastname: Enright
authors.forename: Fariba
authors.initials: F
authors.lastname: Tahami
authors.forename: Sarita
authors.initials: S
authors.lastname: Workman
authors.forename: Ronnie
authors.initials: R
authors.lastname: Chee
authors.forename: A David
authors.initials: AD
authors.lastname: Webster
authors.forename: Richard S B
authors.initials: RS
authors.lastname: Milne
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Emery
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019138:Antibodies, Blocking / Q000494:pharmacology; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D019138:Antibodies, Blocking; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma