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A.B. Nesburn, I. Bettahi, X. Zhu, X. Zhang, A. Mohebbi, A. Vanderberg, B. Holguin, J.V. Jester, S.L. Wechsler, L. BenMohamed; Rabbit Ocular Mucosal Immune System Contain CD4+CD25+ Regulatory T Cells That Control Local and Systemic Herpes Simplex Virus Type 1–Specific T Cell Response . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5139.
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Fighting off the various invading pathogens that constantly attack the ocular surface requires a well–controlled pathogen–specific T–cell response, initiated locally at the ocular mucosal immune system (OMIS). Outside the OMIS, the ability to evoke systemic T cell responses, that are normally suppressed by naturally occurring CD4+CD25+ regulatory T–cells (CD4+CD25+ T reg), has been well documented. To date, there is no report on resident CD4+CD25+ T reg within the OMIS and the role they might play in controlling local ocular immune responses. The purpose of this study was to characterize resident T cells and APCs in normal conjunctiva, a major T cell inductive site of OMIS, and to investigate the role that conjunctiva–derived CD4+CD25+ T reg may play during ocular herpes simplex virus (HSV–1) infection and immunity.
Conjunctiva, cornea, spleen and peripheral blood were harvested from normal and HSV–1 infected rabbits. CD45+ pan leukocytes were sorted and examined by FACS for resident effector and regulatory T cells and APCs. To assess their effect on local and systemic T cell stimulation; CD4+CD25+ T reg and CD4+CD25– non–T reg were isolated from normal conjunctiva and co–cultured in vitro with HSV–specific effector T cells, isolated from immune conjunctiva or PBMC.
Normal conjunctiva contained CD4+ and CD8+ effector T cells, CD4+CD25+ T reg, and CD11b+ and CD11c+ APCs. Surprisingly, CD4+CD25+ T cells were abundant in normal conjunctiva, compared to cornea, spleen and peripheral blood. Moreover, CD4+CD25+ T cells isolated from the normal conjunctiva suppressed HSV–specific T cell responses both locally within the conjunctiva and systemically within the peripheral blood.
These findings shed new light on the immune cell composition and regulation within the OMIS and suggest that conjunctiva–resident CD4+CD25+ T reg cells play a role in controlling ocular mucosal T cell responses. These findings may open new ways to novel immunotherapeutic strategies against pathogens that invade the surface of the eye.
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