Histological and cellular analysis of isolated lymphoid follicles in terminal ileum of long term intestinal transplant recipients, initial report.

MEIER D; CAGNOLA H; CHIRDO F; DOCENA G; RAMISCH D; GONDOLESI G; RUMBO M

Bologna

Congreso; XIth International Small Bowel Transplant Symposium; 2009

International Small Bowel Transplant Symposium

Introduction: Isolated Lymphoid Follicles (ILFs) are small lymphoid structures, located throughout the small intestine, that contribute to gut immune responses. The impact of long term immunosuppressive therapy applied upon intestinal transplantation (ITx) on ILF structures is unknown. We aim to address questions number, structure, and cellular contents of ILF present at the time of ITx ileostomy closure.   Methods: Surgical samples from distal ileum of 5 patients that underwent ileostomy closure operation 15+/-8 months after transplant ITx were studied. Ileal samples from 4 non-ITx operations were included as controls. Surgical specimens were dissected in layers for identification of ILF. Cellular composition of ILF was characterized by immunohistochemistry (IHC) and flow cytometry.   Results: We could not detect differences in the number of ILF present in dissection specimens from ITx patients and normal intestine. A similar density of ILF between 15-20/ cm2 in all cases evaluated with a similar total number of cell counts (average:  100,000 mononuclear cells/ILF) were observed.  ILF were constituted mainly of CD19+CD20+ B cells. Presence of CD4+ and CD8+ T cells, CD11c+ cells and also an architecture of segregated B and T cell zones were evidenced by IHC. Nevertheless, by flow cytometry analysis, 40% percent less CD19+ B cells whereas 45% more CD3+ T cells and 3-times higher percentage of CD8+ T cells in ILF were seen at the time of the ITX ileostomy closure  compared to non ITx patients.   Conclusions: In spite of the long term immunosuppression, ILF are not only present but also within a normal number in the ileal mucosa by the time of ileostomy closure after ITx. However, changes in the B/T cell ratio of ILF after ITx were detected. The analysis of large mucosal samples at the time of the ileostomy closure might be useful to improve our understanding on transplant intestinal immunobiology.