Th17 mediated alloreactivity is facilitated by the pre-transplant microbial burden of the recipient

Abstract

Acute graft-versus-host disease (aGvHD) is a major complication after hematopoietic stem cell transplantation (HSCT) and severity of aGvHD is associated with biological and genetic factors related to donors and recipients. Studies on inflammatory pathways involved in aGvHD have shown a significant impact of the gut microflora on aGvHD development giving increasing evidence in the understanding of the response of innate and adaptive immunity to microbial products. Cytokine deregulation may increase or reduce the risk of aGvHD. Damage of tissues affected by aGvHD reflects the immunological cascade of events in this disease.

Figure 1

(a) HLA-DR expression on antigen presenting cells in the epidermis of the skin (+60 days after HSCT) and (b) HLA-DR expression on colon epithelial cells (+33 days after HSCT) affected by aGvHD (red staining with Permanent Red, magnifications 400x).

Figure 2

Colon biopsy specimen harvested at 33 days after HSCT from patient with clinical symptoms of aGvHD. Hematoxylin and eosin (H+E) staining documented destruction of colon crypts, and immunocytochemistry illustrate CD8+ cells invading damaged crypt epithelium (H+E magnification 200x, red staining with Permanent Red, magnifications 400x).

Figure 3

Colon biopsy specimen harvested at day 63 after HSCT from patient with clinical symptoms of aGvHD. IL-17 producing cells and macrophages CD68+ were seen within cellular infiltrates (brown staining with diaminobenzidine-tetrahydrochloride (DAB) and red staining with Permanent Red, magnifications 400x).