title: Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge.
abstract: Understanding the characteristics of the virus-specific T-lymphocyte response that will confer optimal protection against the clinical progression of AIDS will inform the development of an effective cellular immunity-based human immunodeficiency virus vaccine. We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4(+) T lymphocytes and robust gamma interferon (IFN-gamma)-producing SIV-specific CD8(+) and CD4(+) T-lymphocyte responses. The present studies were initiated to extend these observations to determine which virus-specific T-lymphocyte subpopulations play a primary role in controlling disease progression and to characterize the functional repertoire of these cells. We show that the preservation of the SIV-specific central memory CD8(+) T-lymphocyte population and a linked SIV-specific CD4(+) T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge. Furthermore, we demonstrate that SIV-specific IFN-gamma-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression. These findings underscore the contribution of virus-specific central memory T lymphocytes to controlling clinical progression in vaccinated individuals following a primate immunodeficiency virus infection.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, Boston, MA 02215, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Jörn E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: Adam P
authors.initials: AP
authors.lastname: Buzby
authors.forename: Brianne R
authors.initials: BR
authors.lastname: Barker
authors.forename: Srinivas S
authors.initials: SS
authors.lastname: Rao
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000401:mortality; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma