Immunological Status of Isolated Lymphoid Follicles After Intestinal Transplantation

Abstract

Intestinal transplantation (ITx) faces the challenge of grafting a high immunogenic organ, which is certainly one of the major obstacles for intestinal allograft acceptance. The allograft has to guarantee the proper functioning of the mucosal immune machinery under immunosuppressive conditions. Recently, it has been elucidated that isolated lymphoid follicles (ILFs) are an indispensable part of mucosal immunity to maintain IgA synthesis and consequently to control commensal microflora. No data about these follicular structures in the setting of ITx are available so far. Therefore, we addressed the question whether constitution, integrity and function of allograft ILFs are disturbed by immunosuppressive regimen. We compared allograft ILFs from terminal ileum of transplant patients with ILFs from nontransplant patients via flow cytometry, quantitative real-time polymerase chain reaction and immunohistochemistry. We found that host leukocytes rapidly repopulate allograft ILFs and that maintenance immunosuppressive regimen, tacrolimus and corticosteroids, does not affect their cellular integrity and function. However, allograft ILFs revealed a higher maturation state than control samples and IgA positive plasma cells were increased in number in allograft mucosa. Our results open the path for a better understanding of allograft mucosal immunity.

Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome

“…1C) and donor graft lymphocytes persisted much longer than previously reported (Fig. 1 B-C and S2)( 11, 12 ).…”

“…However, little is known about how HvG and GvH responses influence the turnover, phenotype and repertoire of tissue-resident T-cell populations following transplantation. Studies in mice( 10 ) and humans( 11 ) have indicated that recipient-derived T cells repopulate the GALT (Gut-Associated Lymphoid Tissues) of intestinal allografts early after transplantation. However, the turnover rate of mucosal T cells after intestinal transplantation has been investigated in only a few patients( 12 ) in cross-sectional studies( 11 ), without phenotype or repertoire analysis( 11, 12 ).…”

“…Studies in mice( 10 ) and humans( 11 ) have indicated that recipient-derived T cells repopulate the GALT (Gut-Associated Lymphoid Tissues) of intestinal allografts early after transplantation. However, the turnover rate of mucosal T cells after intestinal transplantation has been investigated in only a few patients( 12 ) in cross-sectional studies( 11 ), without phenotype or repertoire analysis( 11, 12 ). We took advantage of serial protocol biopsies in intestinal transplant recipients to address the hypothesis that recipient cells would replace the donor leukocytes rapidly in the presence of rejection and that homeostatic leukocyte turnover could be measured in the absence of rejection.…”

Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation

“…This has been done previously for investigation of chimerism in peripheral blood after transplantation by our group (28), but previous investigation of chimerism in transplanted intestinal tissue has instead relied on genetic analysis via fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR), or immunohistochemistry (3, 4, 29, 30). Our method allows dynamic and in depth analysis of ILC chimerism and phenotyping.…”

Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation

“…23 Antibodies enrolled in this study are listed in Table 2. Tissue sections were deparaffinized following standard procedures as previously described.…”