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Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa¹

Jamal I. Saada^2,*, Irina V. Pinchuk^2,*,, Carlos A. Barrera^*,, Patrick A. Adegboyega, Giovanni Suarez, Randy C. Mifflin^*, John F. Di Mari^*, Victor E. Reyes^, and Don W. Powell^3,*,¶

^* Department of Internal Medicine, Departments of Neuroscience and Cell Biology, Department of Pathology, Departments of Microbiology and Immunology, and ^¶ Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555

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 -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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK55783), the John Sealy Memorial Endowment Fund, the University of Texas Medical Branch Gastrointestinal Research Interdisciplinary Program, the James W. McLaughlin Endowment Fund, and the Gulf Coast Digestive Diseases Center (DK56338).

² J.I.S. and I.V.P. contributed equally to this publication and should be considered as primary authors.

³ Address correspondence and reprint requests to Dr. Don W. Powell, Department of Internal Medicine, Division of Gastroenterology, University of Texas Medical Branch, Galveston, TX 77555. E-mail address: dpowell{at}utmb.edu

⁴ Abbreviations used in this paper: DC, dendritic cell; SMA, smooth muscle actin; CMF, colonic myofibroblast; AF, Alexa Fluor; SI, stimulation index; HSA, human serum albumin; TT, tetanus toxoid; HEA, human epithelial Ag.

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