Specific aqueous humor factors induce activation of regulatory T cells

PURPOSE. TO examine the possibility that aqueous humor-induced regulatory T cells could function in vivo, these T cells mere examined for their abilit y to suppress adoptive transfer of delayed-type hypersensitivity (DTH). To begin to understand the mechanisms by which aqueous humor induces activatio n of regulatory T cells, alpha-melanocyte stimulating hormone (MSH) and tra nsforming growth factor (TGF)-beta 2 were examined for ability to induce re gulatory T cells. METHODS. Primed T cells were treated with aqueous humor and assayed for reg ulatory activity by injecting them intravenously along with DTH-mediating T cells into syngeneic mice. Antigen-pulsed antigen-presenting cells (APCs) were injected into the pinna of the mouse ear, and swelling was measured 24 hours later. Primed T cells were also activated in vitro in the presence o f alpha-MSH, TGE-beta 1, or TGF-beta 2 and were assayed for proliferation a nd TGF-P production along with suppressing DTH. RESULTS. Aqueous humor-treated T cells suppressed inflammation mediated by DTH T cells. Maximum regulatory T cell activity was induced when primed T c ells were activated in vitro ill the presence of alpha-MSH followed 4 hours later with active TGF-beta 2. Such T cells proliferated, produced TGF-beta , and suppressed DTH, suggesting that alpha-MSH and TGF-beta 2 induce activ ation of regulatory T cells. No regulatory T cell activity could be induced in the presence of TGF-beta 1. CONCLUSIONS. The ocular microenvironment constitutively produces immunoregu latory factors that suppress the induction of inflammatory activity and pro motes regulatory T cell activity. Such regulatory T cells can further contr ibute to maintaining the normal immunosuppressive ocular microenvironment t hrough their ability to suppress activation of other inflammatory T cells.