title: Up-regulation of Tim-3 on T cells during acute simian immunodeficiency virus infection and on antigen specific responders.
abstract: OBJECTIVE
  Understanding the role of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) on T cells and dendritic cells during the course of simian immunodeficiency virus (SIV) infection.
  
  
  METHODS
  Sequentially collected PBMCs from uninfected and SIVmac239-infected rhesus macaques were evaluated for Tim-3 expression by flow cytometry and antigen-specific responses.
  
  
  RESULTS
  Blood innate immune cells (dendritic cells) and B cells showed high constitutive expression of Tim-3, whereas, compared to humans, only a minority of macaque T cells did. However, TIM-3 expression was transiently up-regulated on both CD4 and CD8 T cells during acute SIV infection, correlating with plasma viral loads, CD4 cell counts, and Ki67 expression up to 6 weeks postinfection and returned to baseline values by 8 weeks postinfection. Upon antigen-specific stimulation, most Tim-3 T cells produced various cytokines, suggesting that this marker is up-regulated on effector antigen-specific T cells and not associated with T-cell exhaustion. Among myeloid dendritic cells (mDCs), a clear separation was seen between blood mDCs expressing Tim-3 and those expressing PD-L2 - a ligand for inhibitory receptor programmed death 1.
  
  
  CONCLUSIONS
  Rhesus macaques show constitutive expression of Tim-3 primarily on innate immune cells, but markedly lower levels on T cells compared to humans. Nevertheless, Tim-3 expression on T cells is transiently up-regulated during acute, but not chronic, SIV infection, and appears to be a marker of antigen-specific effector cells. The exact role and contribution of Tim-3 to the modulation of antiviral responses in vivo will require additional investigation.
authors.affiliation: aDepartment of Pathology & Laboratory Medicine, Emory University School of Medicine bDivision of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Amancha
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Hong
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D003713:Dendritic Cells / Q000737:chemistry / Q000821:virology; D005434:Flow Cytometry; D006801:Humans; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000032:analysis*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology*; D013601:T-Lymphocytes / Q000737:chemistry* / Q000821:virology*; D015854:Up-Regulation
chemical_list: D000956:Antigens, Viral; D008565:Membrane Proteins