Specific aqueous humor factors induce activation of regulatory T cells.
OBJECTIVE
To examine the possibility that aqueous humor-induced regulatory T cells could function in vivo, these T cells were examined for their ability to suppress adoptive transfer of delayed-type hypersensitivity (DTH). To begin to understand the mechanisms by which aqueous humor induces activation of regulatory T cells, alpha-melanocyte stimulating hormone (MSH) and transforming growth factor (TGF)-beta2 were examined for ability to induce regulatory T cells.


METHODS
Primed T cells were treated with aqueous humor and assayed for regulatory 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 of alpha-MSH, TGF-beta1, or TGF-beta2 and were assayed for proliferation and TGF-beta 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 cells were activated in vitro in the presence of alpha-MSH followed 4 hours later with active TGF-beta2. Such T cells proliferated, produced TGF-beta, and suppressed DTH, suggesting that alpha-MSH and TGF-beta2 induce activation of regulatory T cells. No regulatory T cell activity could be induced in the presence of TGF-beta1.


CONCLUSIONS
The ocular microenvironment constitutively produces immunoregulatory factors that suppress the induction of inflammatory activity and promotes regulatory T cell activity. Such regulatory T cells can further contribute to maintaining the normal immunosuppressive ocular microenvironment through their ability to suppress activation of other inflammatory T cells.
Nishida
T
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Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Taylor
A W
AW
D019264:Adoptive Transfer; D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000517:prevention & control; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D011817:Rabbits; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D000521:alpha-MSH / Q000494:pharmacology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D000521:alpha-MSH; D010047:Ovalbumin