Expression of B7 molecules in the eye during experimental autoimmune anterior uveitis (EAAU).
OBJECTIVE
We have reported that CTLA4-Fc, a fusion protein that binds B7, prevents the induction of EAAU and reduces the severity of disease in Lewis rats. Since B7.1 and B7.2 have distinctive roles in other autoimmune diseases, we investigated their roles in the development of EAAU.


METHODS
Lewis rats were immunized with melanin associated antigen (MAA). Eyes were collected at different stages of EAAU and the expression of B7 on iris and ciliary body (ICB) cell suspensions determined by flow cytometry analysis. The incidence of EAAU after treatment with anti B7, and the requirement of B7.1 and B7.2 for proliferation and cytokine production of lymphoid cells to MAA were also studied.


RESULTS
B7.2 is up-regulated in resident ICB cells or bone-marrow derived cells which have infiltrated the ICB by day 10 and remains elevated during the acute phase of disease. B7.1 is expressed later during the acute phase. Both B7.1 and B7.2 are down-regulated during remission, with low levels of B7.2 and no detectable B7.1. The incidence of EAAU was reduced by anti-B7.2 treatment and completely inhibited by a combination of both B7.1 and B7.2 antibodies. Neither anti-B7.1 nor anti-B7.2 alone affected proliferation or cytokine production. However, administration of both anti-B7.1 and B7.2 completely inhibited proliferation as well as IL-2 and TNF-alpha production.


CONCLUSIONS
B7.1 and B7.2 are expressed in the eye at different times during EAAU. Both B7 molecules are required for the induction of EAAU, although they probably have different roles.
Shao
Hui
H
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA. h0shao01@louisville.edu
Sun
Deming
D
Sun
Sheher L
SL
Cruze
Jose Maria
JM
Bora
N
N
Kaplan
Henry J
HJ
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen; D002417:Cattle; D002454:Cell Differentiation / Q000276:immunology; D002924:Ciliary Body / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005434:Flow Cytometry / Q000379:methods; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000096:biosynthesis; D007498:Iris / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008543:Melanins / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy
D000906:Antibodies; D000941:Antigens; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008543:Melanins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D013936:Thymidine