INVESTIGADORES
RUMBO Martin
congresos y reuniones científicas
Título:
Immunosuppressive therapy does not affect cellularity and function of isolated lymphoid follicles after human intestinal transplantation
Autor/es:
DOMINIK MEIER; GUILLERMO DOCENA; DIEGO RAMISCH; GABRIEL GONDOLES; MARTIN RUMBO
Reunión:
Congreso; XII International Small Bowel Transplantation Symposium; 2011
Resumen:
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Introduction: Isolated lymphoid follicles (ILF)
are organized structures that function as inductive sites contributing to intestinal
IgA production. Increased numbers of lymphoid aggregates were detected in
inflammatory bowel disease. However, no studies have been conducted about the behavior
of ILF after intestinal transplantation (ITx) in humans. We aimed to isolate
ILF from human intestinal allografts and to elucidate the impact of immunosuppressive
therapy on ILF structure and function. Material and Methods: 10
full thickness biopsies of distal ileum were obtained, 5 at the time of the
ileostomy closure, (ITx group, all under steroids and tacrolimus); and 5 at
ileal segmental resection in non-Tx patients (Control group). To isolate ILF,
mucosa and submucosa were dissected from the muscular layer, then the epithelial
monolayer were removed by EDTA treatment to finally obtained the ILFs. ILF surface
density was measured. ILF were collected and homogenized for immune cell
analysis by flow cytometry (markers used: CD3, CD4, CD8, CD19, CD56, CD69) and activation
induced cytidine deaminase (AID), a gene that is critical for class
switch recombination, was measured by qPCR. Formaldehyde-fixed and
paraffin-embedded tissue was used for immunohistological analysis. Results:
A non-significant increase of ILF numbers/cm2 between ITx group (mean 3±1.8) and Control group (mean 1.84±0.9) was observed.
No significant changes among the different percentages of subpopulations (CD4+
and CD8+ T, CD19+ B, CD56+ NK, CD3+
CD56+ NKT cells) were seen in both groups. The relative expression
of AID was increased in ILF compared to lamina propria in both groups
(mean fold increase was 21±15 for ITx group
vs. 106±56 for Control group). Finally,
immunohistological analysis showed a similar distribution of IgA positive
plasma cells in lamina propria from ITx and Control groups sections. Conclusions:
Our results reveal for the first time that ILF can be isolated and further
analyzed in samples obtained after ITx. The standard immunosuppressive therapy does
not seem to affect cellularity and functional capacity of immunoglobulin class
switch of ILF. We could not detect any sign of increased activation in ILF from
allograft specimen. Further studies of allograft ILF would contribute to better
understand the immunobiology of intestinal transplantation.