title: Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer.
abstract: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replication in vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103-111 RM9, Gag389-394 GW9, Env338-346 RF9, and Nef254-262 LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir.
  
  
  OBJECTIVE
  CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques. This is an important first step toward the development of autologous transfer strategies to explore cellular immunity and potential therapeutic applications in the SIV model.
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Mariel S
authors.identifier: http://orcid.org/0000-0002-3609-8447
authors.initials: MS
authors.lastname: Mohns
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Cain
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Ngoc H
authors.initials: NH
authors.lastname: Pham
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA doconnor@primate.wisc.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018929:Cell Culture Techniques / Q000379:methods; D002469:Cell Separation / Q000379:methods; D016207:Cytokines / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D008252:Macaca fascicularis / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load
chemical_list: D016207:Cytokines