Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa

Abstract

The human gastrointestinal mucosa is exposed to a diverse normal microflora and dietary Ags and is a common site of entry for pathogens. The mucosal immune system must respond to these diverse signals with either the initiation of immunity or tolerance. APCs are important accessory cells that modulate T cell responses which initiate and maintain adaptive immunity. The ability of APCs to communicate with CD4+ T cells is largely dependent on the expression of class II MHC molecules by the APCs. Using immunohistochemistry, confocal microscopy, and flow cytometry, we demonstrate that α-smooth muscle actin+, CD90+ subepithelial myofibroblasts (stromal cells) constitutively express class II MHC molecules in normal colonic mucosa and that they are distinct from professional APCs such as macrophages and dendritic cells. Primary isolates of human colonic myofibroblasts (CMFs) cultured in vitro were able to stimulate allogeneic CD4+ T cell proliferation. This process was dependent on class II MHC and CD80/86 costimulatory molecule expression by the myofibroblasts. We also demonstrate that CMFs, engineered to express a specific DR4 allele, can process and present human serum albumin to a human serum albumin-specific and DR4 allele-restricted T cell hybridoma. These studies characterize a novel cell phenotype which, due to its strategic location and class II MHC expression, may be involved in capture of Ags that cross the epithelial barrier and present them to lamina propria CD4+ T cells. Thus, human CMFs may be important in regulating local immunity in the colon.

Monocyte Chemoattractant Protein-1 Production by Intestinal Myofibroblasts in Response to Staphylococcal Enterotoxin A: Relevance to Staphylococcal Enterotoxigenic Disease

“…In contrast to constitutive expression of MHC class II in vivo, the expression of these molecules on primary myofibroblast isolates is drastically reduced during in vitro passages. However, treatment of colonic IMF with low doses of IFN-␥ significantly increases MHC class II expression (27). Similar to our previous findings, in this study, we first confirmed that IFN-␥ treatment maximizes MHC class II expression on small intestinal IMF primary cultures.…”

“…We recently demonstrated that class II ϩ colonic myofibroblasts can function as nonprofessional APCs for allogeneic and Ag-specific T cell activation (27). In contrast to constitutive expression of MHC class II in vivo, the expression of these molecules on primary myofibroblast isolates is drastically reduced during in vitro passages.…”

“…We recently reported that subepithelial IMFs constitutively express MHC class II in the normal colon (26,27). In the studies presented herein, we evaluated whether human subepithelial IMFs can be among the initiators of the local intestinal inflammatory responses to staphylococcal enterotoxins.…”

“…IMFs were stained for various surface markers. Single-color immunostaining was performed according to a standard surface FACS staining BD Pharmingen protocol as described previously (27). Flow cytometry analysis was performed using FACScan and FACSCanto cytometers (BD Biosciences).…”

Histomorphometric study of role of lactoferrin in atrophy of the intestinal mucosa of rats

“…Some show their beneficial features [39][40][41][42][43] and others cite harmful activities [44][45][46].…”