title: HIV patients on antiretroviral therapy have high frequencies of CD8 T cells specific for Immediate Early protein-1 of cytomegalovirus.
abstract: OBJECTIVE
  To assess the frequency and phenotype of cytomegalovirus (CMV)-specific CD8 T cells in previously immunocompromised HIV patients with stable undetectable HIV viremia due to highly active antiretroviral therapy (HAART).
  
  
  METHODS
  Twenty-one CMV-seropositive HIV patients with nadir CD4 T-cell counts < 50 x 10(6) cells/l, at least 4 years on HAART and 6 months of complete viral suppression (< 50 HIV RNA copies/ml) and 12 CMV-seropositive, HIV-seronegative age/sex-matched controls were studied. CD4 and CD8 T-cell responses to whole CMV and two HLA-A*02 restricted CMV peptides [NLV from pp65 and VLE from Immediate Early 1 (IE1)] were measured by interferon (IFN)gamma ELISpot. Phenotypes of peptide-specific CD8 T cells were determined by tetramer staining.
  
  
  RESULTS
  In the ELISpot assay, HIV patients had significantly more CD8 T cells producing IFN gamma in response to VLE than controls, whereas numbers of NLV-specific and CMV-specific IFN gamma spots were similar. Four HIV patients and one control had large VLE and/or NLV-specific CD8 T-cell populations despite the absence of CMV-specific CD4 T cells. The majority of peptide-specific CD8 T cells from HIV patients and controls were CD28-, CD45RO+ and CD45RA-. However, a significantly higher proportion of VLE-specific CD8 T cells expressed perforin compared to NLV-specific CD8 T cells in HIV patients.
  
  
  CONCLUSIONS
  HIV patients had elevated numbers of IE1-specific, IFNgamma-producing perforin-positive CD8 T cells compared to controls. As IE1 is expressed early during CMV reactivation, these cells may be important for preventing CMV replication to pathogenic levels. In addition, CMV-specific CD4 T cells are not essential for maintenance of large populations of CMV-specific CD8 T cells in aviremic HIV patients on HAART.
authors.affiliation: Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Western Australia. sfstone@graduate.uwa.edu.au
authors.forename: Shelley F
authors.initials: SF
authors.lastname: Stone
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
authors.forename: Naeem
authors.initials: N
authors.lastname: Khan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Moss
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000032:analysis*; D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000821:virology*; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: D000956:Antigens, Viral; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; C044582:immediate-early proteins, cytomegalovirus; D054353:Perforin