title: Antigen burden is major determinant of human immunodeficiency virus-specific CD8+ T cell maturation state: potential implications for therapeutic immunization.
abstract: The majority of untreated human immunodeficiency virus (HIV) type 1-infected individuals ultimately develop uncontrolled viremia and progressive disease. Cytotoxic T lymphocytes (CTLs) are known to play an important role in controlling HIV-1 replication, which has led to an increasing interest in augmenting conventional antiretroviral therapy with therapeutic vaccination. The successful development of a therapeutic vaccine will rely on the ability to correlate an aspect of the immune response with clinical outcome. In this study, the CD8(+) T cell maturation status of antigen-specific cells in models of well and poorly controlled virus infections were compared, to show that a memory phenotype predominates when antigen loads are absent or low. In HIV-1 infection, the emergence of memory CD8(+) T cells was found to occur only in individuals with highly suppressed viral replication for an extended duration. Such assessments of the immune response may provide a refined measure of virus control.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania 19486, USA. lynda_tussey@merck.com
authors.forename: Lynda G
authors.initials: LG
authors.lastname: Tussey
authors.forename: Ushasree Sadasivan
authors.initials: US
authors.lastname: Nair
authors.forename: Margaret
authors.initials: M
authors.lastname: Bachinsky
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Edwards
authors.forename: Janna
authors.initials: J
authors.lastname: Bakari
authors.forename: Karen
authors.initials: K
authors.lastname: Grimm
authors.forename: Joseph
authors.initials: J
authors.lastname: Joyce
authors.forename: Rupert
authors.initials: R
authors.lastname: Vessey
authors.forename: Roy
authors.initials: R
authors.lastname: Steigbigel
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006678:HIV / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008297:Male; D019562:Viral Load; D014780:Viruses / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D015488:HIV Antigens