title: Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues.
abstract: BACKGROUND
  Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors).
  
  
  RESULTS
  Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites.Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated.
  
  
  CONCLUSIONS
  A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We conclude, that a robust SIV-specific mucosal immune response seems to be essential for establishing and maintaining the controller status and consequently for long-term survival.
authors.affiliation: Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Goettingen, Germany. tschultheiss@dpz.eu
authors.forename: Tina
authors.initials: T
authors.lastname: Schultheiss
authors.forename: Reiner
authors.initials: R
authors.lastname: Schulte
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sauermann
authors.forename: Wiebke
authors.initials: W
authors.lastname: Ibing
authors.forename: Christiane
authors.initials: C
authors.lastname: Stahl-Hennig
mesh_terms: D000818:Animals; D001769:Blood / Q000821:virology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000821:virology; D018928:Immunity, Mucosal; D008168:Lung / Q000821:virology; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016207:Cytokines