title: Comparisons of CD8+ T cells specific for human immunodeficiency virus, hepatitis C virus, and cytomegalovirus reveal differences in frequency, immunodominance, phenotype, and interleukin-2 responsiveness.
abstract: To better understand the components of an effective immune response to human immunodeficiency virus (HIV), the CD8(+) T-cell responses to HIV, hepatitis C virus (HCV), and cytomegalovirus (CMV) were compared with regard to frequency, immunodominance, phenotype, and interleukin-2 (IL-2) responsiveness. Responses were examined in rare patients exhibiting durable immune-mediated control over HIV, termed long-term nonprogressors (LTNP) or elite controllers, and patients with progressive HIV infection (progressors). The magnitude of the virus-specific CD8(+) T-cell response targeting HIV, CMV, and HCV was not significantly different between LTNP and progressors, even though their capacity to proliferate to HIV antigens was preserved only in LTNP. In contrast to HIV-specific CD8(+) T-cell responses of LTNP, HLA B5701-restricted responses within CMV pp65 were rare and did not dominate the total CMV-specific response. Virus-specific CD8(+) T cells were predominantly CD27(+)45RO(+) for HIV and CD27(-)45RA(+) for CMV; however, these phenotypes were highly variable and heavily influenced by the degree of viremia. Although IL-2 induced significant expansions of CMV-specific CD8(+) T cells in LTNP and progressors by increasing both the numbers of cells entering the proliferating pool and the number of divisions, the proliferative capacity of a significant proportion of HIV-specific CD8(+) T cells was not restored with exogenous IL-2. These results suggest that immunodominance by HLA B5701-restricted cells is specific to HIV infection in LTNP and is not a feature of responses to other chronic viral infections. They also suggest that poor responsiveness to IL-2 is a property of HIV-specific CD8(+) T cells of progressors that is not shared with responses to other viruses over which immunologic control is maintained.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Jagannathan
authors.forename: Christine M
authors.initials: CM
authors.lastname: Osborne
authors.forename: Cassandra
authors.initials: C
authors.lastname: Royce
authors.forename: Maura M
authors.initials: MM
authors.lastname: Manion
authors.forename: John C
authors.initials: JC
authors.lastname: Tilton
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Steven
authors.initials: S
authors.lastname: Fischer
authors.forename: Claire W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: Julia A
authors.initials: JA
authors.lastname: Metcalf
authors.forename: Mary
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Matthew
authors.initials: M
authors.lastname: Pipeling
authors.forename: John F
authors.initials: JF
authors.lastname: McDyer
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Manley
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Meier
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.forename: Laura
authors.initials: L
authors.lastname: Hertel
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015235:HLA-B Antigens / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D015235:HLA-B Antigens; C484830:HLA-B*57:01 antigen; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens