title: Hematopoietically derived retinal perivascular microglia initiate uveoretinitis in experimental autoimmune uveitis.
abstract: BACKGROUND
  Hematopoietically derived cells in the retina were studied for the expression of molecules associated with antigen presentation.
  
  
  METHODS
  Bone marrow cells of (Lewis x Brown Norway) F1 rats (LBNF1) were transplanted to sublethally irradiated Brown Norway (BN) rats to construct chimeric rats (LBNF-->BN). Each of 21 established chimeras received an adoptive transfer of uveitogenic Lewis T lymphocytes. Three rats were killed on each of 7 consecutive days. The right eye of each rat was processed for flat-mount preparation of the retina; the left eye of each was frozen for cryostat sectioning. All tissues were then stained with one of the following antibodies: OX-3 (Lewis-specific MHC class II marker), anti-ICAM, anti-B7- 1, anti-TNF-alpha or anti-IL-1beta.
  
  
  RESULTS
  Initial clinical signs of EAU appeared first on day 4; by day 6, full-blown EAU was noted. The flatmount preparations revealed the presence of OX-3+ cells in the retina, perivascularly exhibiting dendritic morphology on day 2. These cells were observed in the retinal nerve fiber layer (NFL). No B7-1+, ICAM-1+, TNF-alpha+ or IL-1beta + cells were detected. Cryostat sections revealed positive cell staining of perivascular microglia and astrocytes in the retinal NFL with anti-IL-1beta and anti-TNF-alpha antibodies.
  
  
  CONCLUSIONS
  Since only perivascular bone marrow-derived cells are seen to express MHC class II molecules prior to onset of EAU, and since these cells also generate the cytokines IL- 1beta and TNF-alpha, it appears that initial presentation of antigen in the retina could be by these cells.
authors.affiliation: Department of Ophthalmology, University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Gullapalli
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Pararajasegaram
authors.forename: N A
authors.initials: NA
authors.lastname: Rao
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D018122:B7-1 Antigen / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000032:analysis; D019084:Fluorescent Antibody Technique, Indirect; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D009836:Oligodendroglia / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012160:Retina / Q000276:immunology*; D012173:Retinitis / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000473:pathology
chemical_list: D018122:B7-1 Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1