Effect of the ocular microenvironment in regulating corneal dendritic cell maturation.
OBJECTIVE
To determine whether the ocular anterior segment (aqueous humor and cornea) actively inhibits dendritic cell (DC) maturation.


METHODS
Dendritic cells were injected into syngeneic corneas or conjunctivae, and their surface major histocompatibility complex class II expression in response to the local milieu was assessed using confocal microscopy. Immature DCs were cocultured with corneal supernatant or with aqueous humor to evaluate their regulation of DC phenotypic and functional maturity.


RESULTS
In contrast to conjunctivally injected DCs, DCs injected into the cornea resisted up-regulation in expression of surface major histocompatibility complex class II. Corneal supernatant-treated and aqueous humor-treated DCs retained their immaturity, as reflected by high antigen uptake but low costimulatory molecule (CD80 and CD86) expression and poor T-cell stimulation. Anti-transforming growth factor beta(2) treatment of aqueous humor and of corneal supernatant led to complete and partial blockade of their inhibition of DC maturation, respectively. However, alpha-melanocyte-stimulating hormone and calcitonin gene-related peptide had no demonstrable effect on DC maturation.


CONCLUSIONS
Cornea and aqueous humor, principally through transforming growth factor beta(2,) promote generation of phenotypically and functionally immature DCs. Clinical Relevance Our results indicate that relative immune quiescence in the cornea and in the anterior segment is actively maintained in part by the inhibitory effect of transforming growth factor beta(2) on resident DCs and by their suppression of T-cell-mediated immune and inflammatory responses.
Shen
Linling
L
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Barabino
Stefano
S
Taylor
Andrew W
AW
Dana
M Reza
MR
D000818:Animals; D001082:Aqueous Humor / Q000502:physiology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D018920:Coculture Techniques; D003315:Cornea / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010641:Phenotype; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D053781:Transforming Growth Factor beta2; D000521:alpha-MSH; D015740:Calcitonin Gene-Related Peptide