T-Lymphocyte Migration is Differently Regulated in Appendiceal Lymph
Follicles and Intestinal Peyer’s Patches
Yoshikazu Tsuzuki, Hideyasu Nagamatsu, Koji Matsuzaki, Ryota Hokari, Kazuro Itoh, and Soichiro Miura
Key words. T lymphocyte, Appendix, MAdCAM-1, ICAM-1
Appendix as an Inductive Site of Intestinal Inflammation
The appendix was long considered a redundant organ. However, thereafter, analysis of immune components of the appendix revealed that slightly fewer than one third of its cells are T cells and that normal adult appendiceal lym- phocyte reactivity is predominated by helper T cells [1]. In addition, the appendix has been reported to be involved in intestinal inflammation. For example,“skip lesions” of the appendix were detected in ulcerative colitis (UC) specimens examined [2], and discontinuous appendiceal involvement was found in patients undergoing proctocolectomy for UC [3]. As regards the mechanisms in appendiceal inflammation, Bittinger et al. demonstrated a different expression of cell adhesion molecules by endothelial (EC) and mesothelial cells (MC) in the various stages of appendicitis, with early E- selectin and intercellular cell adhesion molecule-1 (ICAM-1) expression in EC, followed by vascular cell adhesion molecule (VCAM-1) in EC and MC [4], suggesting that adhesion molecules play pivotal roles in appendiceal inflam- mation. In addition, recently, potential roles of chemokines and their recep- tors in lymphocyte migration have been reported.
On the other hand, preventive effects of appendectomy for UC have been reported in a clinical setting [5–8]. Moreover, in an experimental model of young T-cell receptor (TCR)-a deficient mice, removal of the appendix inhib- ited the induction of experimental colitis [9]. In another experimental model,
243 Second Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
including the dextran sulfate sodium (DSS)-induced colitis model, appen- dectomy affords protection against colitis [10].
Although lymph follicles of the appendix (ALFs) play an important role as a secondary lymphoid tissue as described above, the characteristics of lym- phocyte trafficking have not been investigated in the appendix. Therefore, we investigated T lymphocyte–endothelial interactions in ALFs compared with those in Peyer’s patches (PPs) using an intravital microscope and investigated the contribution of adhesion molecules, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and ICAM-1, and the role of chemokines in the context of the comparison with that in intestinal PPs [11].
Intravital Observation of Lymphocyte Migration in ALFs
For the preparation of T lymphocytes, spleen and mLNs of BALB/c mice were minced and T-cell-rich fraction was obtained by T-cell separation columns.
Thereafter, T lymphocytes were labeled with CFSE solution. The intestine was exteriorized, an appendix and parts of small intestine were ligated, and CFSE- labeled T lymphocytes were injected via a tail vein. Behavior of T lympho- cytes was observed from the serosal side by an intravital microscope at three sites (ALF, ileal PP, and jejunal PP) in the same animal and recorded for 90 min. In some sets of experiments, anti-MAdCAM-1 monoclonal antibody (mAb), anti-ICAM-1 mAb, or a control rat IgG was injected 30 min before the infusion of T lymphocytes.
The percentage of rolling lymphocytes in microvessels of ALFs was not significantly different from that in PPs in small intestine. However, the administration of anti-MAdCAM-1 mAb significantly inhibited lymphocyte rolling in ALFs, but not in intestinal PPs. We also found that the number of adherent T lymphocytes was remarkably suppressed by anti-MAdCAM-1 mAb at these three sites. On the other hand, anti-ICAM-1 mAb significantly suppressed T-lymphocyte adherence at 50 min only at the appendix, but not PPs. Finally, chemokine receptor CCR7 was shown to play an important role in T-lymphocyte adherence in all sites. These results suggest the possibility that T-lymphocyte migration is differently regulated in ALFs and intestinal PPs.
References
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