title: Induction of a virus-specific effector-memory CD4+ T cell response by attenuated SIV infection.
abstract: We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVDeltanef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4-10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5-10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIVDeltanef animals were predominantly CD27-CD28-CD45RAlowCCR7-CCR5-, consistent with an effector-memory subset, and included a fully differentiated CD45RA+CCR7- subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RA-CCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7-CD4+ subset from SIVDeltanef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector-memory T cell population. The ability of SIVDeltanef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, and Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, Boston 02115, USA. mcgauduin@sfbr.org
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gauduin
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu
authors.forename: Amy
authors.initials: A
authors.lastname: Barabasz
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Mike
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002908:Chronic Disease; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*