Hematopoietically derived retinal perivascular microglia initiate uveoretinitis in experimental autoimmune uveitis.
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.
Gullapalli
V K
VK
Department of Ophthalmology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Zhang
J
J
Pararajasegaram
G
G
Rao
N A
NA
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
D018122:B7-1 Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1