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Updated: Aug 8, 2026
Induction of Intestinal Graft-versus-host Disease and Its Mini-endoscopic Assessment in Live Mice
Published on: February 11, 2019
Cellular blebbing in superficial colonic epithelial cells occurring with murine graft-versus-host disease
M L Eigenbrodt1, J S Kneitz, D L Thiele
1Department of Pathology and Laboratory Medicine, University of Texas Medical School, Houston 77030, USA.
Insights
Subnuclear blebbing, a rare microscopic change in graft-versus-host disease (GVHD), was observed in mouse models. This finding suggests blebbing may precede severe intestinal damage in GVHD.
Area of Science:
- Gastroenterology
- Immunology
- Pathology
Background:
- Graft-versus-host disease (GVHD) can cause significant gastrointestinal damage.
- Microscopic changes in the colonic epithelium during GVHD are not fully understood.
- Subnuclear blebbing is a rarely described phenomenon in GVHD.
Purpose of the Study:
- To investigate subnuclear blebbing in the colonic epithelium in a murine model of GVHD.
- To evaluate the severity of GVHD-induced changes and their association with epithelial damage.
- To identify the T cell subsets involved in mediating these changes.
Main Methods:
- Utilized a murine model of GVHD involving transfer of T cell subsets to allogeneic recipients.
- Employed light and electron microscopy to examine colonic epithelial changes.
- Assessed the severity of GVHD and correlated it with observed histological alterations.
Main Results:
- Subnuclear blebbing was observed in the basal region of superficial enterocytes.
- Microscopically, blebs appeared as organelle-poor, cytoplasm-filled protrusions.
- CD4+-enriched, CD8+-depleted T cells were capable of inducing blebbing, suggesting a role for cytokine responses.
Conclusions:
- Subnuclear blebbing is a distinct microscopic feature associated with GVHD in the colon.
- The findings suggest that helper T cells may mediate this epithelial change.
- Blebbing is potentially a precursor lesion to epithelial erosion and ulceration in severe intestinal GVHD.
Abstract:
Subnuclear blebbing of the superficial colonic epithelium, a rarely described light and electron microscopic change in graft-versus-host disease (GVHD), was studied in a murine model of GVHD. Severity of changes induced by transfer of various donor T cell subsets to irradiated, allogeneic recipients, and association with more severe alterations such as erosions and ulceration were evaluated. By light microscopy the basal region of the superficial enterocytes was greatly expanded by eosinophilic to amphophilic, flocculent, sometimes vacuolated material. By electron microscopy these changes were found to be organelle-poor, cytoplasm-filled protrusions from the basal surface of the epithelium. In this model, helper T cells (CD(4+)-enriched, CD(8+)-depleted T cells) transplanted after high dose irradiation were capable of causing the change suggesting cytokine responses may be involved in mediating the cellular injury seen histologically. Close association of blebbing and erosions suggest the blebbing may be the precursor to epithelial erosion or denudation seen in severe intestinal GVHD.
