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S. K. Chauhan, D. R. Saban, R. Dana; Regulatory T Cell Compartmentalization in Corneal Allograft Recipients. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2506.
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Appropriate homing and migration are the pre-requisites for efficient functioning of immune cells in vivo. We herein investigate the homing behavior of Foxp3+ regulatory T cells (Tregs) in corneal allograft recipients and the expression patterns of different homing receptors by Tregs.
Fully disparate corneal grafts from C57Bl/6 (H-2b) mice were orthotopically transplanted onto BALB/c (H-2d) recipient mice. Regional draining lymph nodes (dLN) and grafted corneas were harvested from syngeneic recipients, allograft acceptors, and allograft rejectors at week 3 post-transplantation. Tregs from dLN and corneas of different groups were analyzed for CC chemokine receptor 7 (CCR7) and αE integrin (CD103) expression using flow cytometry.
The frequency of Tregs in both the dLN and grafted corneas (10-12%) was comparable among different graft recipient groups. Nearly all (>95%) the dLN-Tregs of different groups expressed CCR7, albeit at different levels. In allograft acceptors approximately 55% of dLN-Tregs were CCR7high as compared to 27% in allograft rejectors and syngeneic recipients. CD103 was only expressed by less than 16% of dLN-Tregs in all the different groups. A majority of cornea-infiltrating Tregs in all the transplanted groups were also found positive for CCR7, but expression levels were much lower compared to dLN-Tregs. Unlike dLN-Tregs, half of the cornea-infiltrating Tregs (45-50%) expressed CD103 in all the recipient groups.
Our data demonstrate that Tregs in different compartments of graft recipients differentially express CCR7 and αE integrin which may be essential for their specific homing to lymphoid tissues and graft sites, respectively. In addition, CCR7high expression by dLN-Tregs may account for their enhanced functional activity in vivo.
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