Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa.
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 alpha-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.
Saada
Jamal I
JI
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Pinchuk
Irina V
IV
Barrera
Carlos A
CA
Adegboyega
Patrick A
PA
Suarez
Giovanni
G
Mifflin
Randy C
RC
Di Mari
John F
JF
Reyes
Victor E
VE
Powell
Don W
DW
D000199:Actins / Q000032:analysis; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D003106:Colon / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D004848:Epithelium / Q000737:chemistry / Q000276:immunology; D005347:Fibroblasts / Q000737:chemistry / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018613:Microscopy, Confocal; D009092:Mucous Membrane / Q000276:immunology; D032390:Myoblasts, Smooth Muscle / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D017154:Stromal Cells / Q000737:chemistry / Q000276:immunology; D018800:Thy-1 Antigens / Q000032:analysis
D000199:Actins; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D018800:Thy-1 Antigens; D007371:Interferon-gamma