Ia
− DC precursors have been identified in the mouse blood,
9 and spleen.
46 In addition, a distinct DC precursor that precedes development of mature and immature DCs has recently been characterized that is CD11c
+CD11b
+.
49 This subset of DC precursors has been suggested to correspond to the human CD1a
−CD14
+ DC precursor,
50 that coexpresses the CD34 progenitor marker, which was also recently detected in the corneal stroma.
51 There are two different pathways that lead to the generation of myeloid DCs. DCs can branch off early within the myeloid lineage and then appear as immature DCs, as they express a low level of MHC class II. Alternatively, DCs and monocytes/macrophages can develop from a more differentiated monocyte termed an “indeterminate” cell.
52 53 Staining of the stroma for CD14, a myeloid cell surface marker that designates relative immaturity, demonstrated a significant number of cells stained for this marker. These CD14
+ cells were present throughout all layers of the stroma, both in the periphery and in the center. CD11c
+CD11b
+ DCs in the anterior stroma stained CD14
dim, which further confirmed their myeloid lineage. Cells that stained CD14
bright in the stroma, were, however, mostly CD11c
−, thereby likely belonging to an even less differentiated form of precursor BM-derived cells. The presence of an undifferentiated precursor DC, would be similar to the recent finding of DC precursors in the central nervous system,
54 where these cells can be skewed toward a more DC or macrophage-like profile in response to different factors. Thus, in contrast to other organs, where terminally differentiated populations of resident DCs and/or macrophages outnumber colonizing precursors, large numbers of DCs within the cornea (and the central nervous system) remain in an undifferentiated state. Whether these stromal cells represent an additional line of immunologic defense other than the epithelial LCs and whether they play a role in induction of tolerance and the immune-privileged state of these tissues remain to be determined.