Phenotypic and immunoregulatory characteristics of monocytic iris cells

Abstract

Summary The introduction of antigen into the anterior chamber of an eye induces the antigen‐specific suppression of cell‐mediated immunity and the antigen‐induced production of immunoglobulin G2 antibodies. To define further the role of iris monocytic cells in the systemic suppression of cell‐mediated immunity that follows the entry of foreign antigen into the anterior chamber, murine iris wholemounts or cell suspensions of iris cells were stained with fluorescent anti‐F4/80 and/or anti‐CD11c, anti‐CD11b antibodies and examined by confocal microscopy or flow cytometry, respectively. Monocytic cells in iris cell suspensions were recovered from mice receiving an injection of trinitrophenylated bovine serum albumin (TNP‐BSA) into an anterior chamber and Percoll‐enriched iris cells separated into cells expressing F4/80 or CD11c were injected intravenously into TNP‐BSA‐immunized or naive recipients. The recipients were challenged to induce delayed‐type hypersensitivity (DTH) or were provided with splenocytes or thymocytes that transfer the suppression of DTH. The homing of monocytic bone marrow cells to the iris was determined by the intravenous injection of bone marrow cells from green fluorescent protein (GFP)‐transgenic donors into C57 mice, and the staining of recipient iris wholemounts with anti‐F4/80 antibodies. Iris cells with a dendritic morphology expressing both F4/80 and/or CD11c and CD11b, some cells expressing only F4/80 or CD11c, were detected. The irides of irradiated GFP– mice that received intravenous GFP+ bone marrow cells contained GFP+ F4/80+ cells. F4/80+ and CD11c+ cells from the irides of donors that received intracameral TNP‐BSA transferred the suppression of DTH when injected intravenously into TNP‐BSA‐immunized recipients, activated immunoregulatory thymocytes and activated antigen‐specific splenic regulatory effector cells. These results support the hypothesis that iris monocytic cells may participate in the systemic induction of regulatory T cells.

Immune regulation and the eye

“…A popular posit is that during ACAID induction, the antigen that is injected into the eye is picked up by indigenous F4/80 + cells, carried through the trabecular meshwork into the bloodstream, and after a possible detour into the thymus [24][25][26] the APC associated antigen makes its way into the spleen. Within the spleen the F4/80 + APC interact with T cells, NKT cells and marginal zone B cells to induce antigen-specific Treg cells that limit both local and systemic Th1 and Th2 response ( Figure 2).…”

The suppression of hypersensitivity by ocular‐induced CD8+T cells requires compatibility in the Qa‐1 haplotype

“…As such it is useful to investigate the nature and mechanisms of systemic regulatory T cells induced by the injection of antigen into the AC. Although CD8 + regulatory T cells induced by the intracameral injection of antigen (AC‐SPL cells) suppress cell‐mediated immunity effected by immunized T cells, 12 , 13 , 14 , 15 several cell types participate in the induction of the CD8 + regulatory splenic T cells after the injection of antigen into the AC 7 , 12 , 13 , 14 , 16 , 17 , 18 , 19 , 20 . Moreover, the activation of splenic CD8 + regulatory T cells by intracameral antigen is restricted by Qa‐1 antigens expressed by B cells that present antigen to CD8 + T cells 20 .…”

An Intracameral Injection of Antigen Induces In Situ Chemokines and Cytokines Required for the Generation of Circulating Immunoregulatory Monocytes

“…Naïve F4/80 + monocytes associated with the iris and circulating F4/80 + monocytes from naïve or immunized mice do not induce antigen-specific regulatory T cells that suppress DTH [1], [2], [8]–[10]. Moreover, aqueous humor and antigen will induce such immunoregulatory monocytes ex vivo [9], [23].…”