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Hermann J Rothkötter

Publications and source records attributed to Hermann J Rothkötter.

4 recordsLinked to original sources

Lymphocyte migration studies.

For maintenance of immunity and tolerance, the organs and tissues of the organism are connected by migrating lymphoid cells. Understanding lymphocyte migration is essential for many disorders and diseases-- especially in the mucosa-lined organs. Detailed analyses of migrating lymphocytes have been performed in many species, especially in laboratory animals. However, important experiments in lymphocyte migration have been carried out in large animals, for example sheep, cattle and pigs. These species allow experimental procedures like in situ-organ labelling, lymphocyte retransfusion studies or lymph vessel cannulations. Such studies have made an important contribution to the understanding of the overall principles of lymphocyte migration especially in the mucosal immune system. Major results on the specific migration of naïve and memory T cells through lymphoid organs, the re-distribution of gamma/delta T cells in the intestinal immune system and the emigration of newly produced B cells from the ileal Peyer's patches have been obtained in large animals. Since there are growing numbers of markers for large animals, and molecular biology methods are available in these species, experiments in large animals will be an essential tool for the understanding of lymphocyte migration especially in mucosal organs.

Animals↗

Proliferating intestinal gamma/delta T cells recirculate rapidly and are a major source of the gamma/delta T cell pool in the peripheral blood.

The proliferation, recirculation and repertoire of gut-derived gamma/delta T cells were studied in pigs in vivo. Proliferating gamma/delta T cells (detected by BrdU labeling) are present in all intestinal compartments. In the gut lymph approximately 0.5% of all gamma/delta T cells were proliferating. These gut-derived BrdU(+) gamma/delta T cells re-enter the intestinal tissues, and re-appear in the intestinal lymph far more often than other cells: about 22% of i.v.-injected BrdU(+) gamma/delta T cells were recovered again from the intestinal lymph within 72 h (compare with BrdU(+) B cells 2%, and other BrdU(+) T cells 10%). The contribution of the gut to the migrating gamma/delta T cell pool in the blood became obvious: the proportion of BrdU(+) gamma/delta T cells was three-times larger in control versus cannulated pigs. In 9-month-old pigs, clonally expanded T cells were identified in the intestine by complementarity-determining region 3 spectratyping of TCR-delta transcripts. Such expansions were not visible in the blood or intestinal lymph. The distribution of gamma/delta T cells within the intestinal tract is likely to depend to a large degree on the proliferation and the migratory properties of these cells which are different to those of alpha/beta T cells and B lymphocytes.

Animals↗

Development and compartmentalization of the porcine TCR delta repertoire at mucosal and extraintestinal sites: the pig as a model for analyzing the effects of age and microbial factors.

gammadelta T cells are an important component of the mucosal immune system. Previously, we have shown that the TCR delta repertoire in human intestine is polyclonal at birth and becomes increasingly restricted with age. In this study, we expand those studies to the pig which allows more extensive experiments including several organs. Tissues from different mucosal sites like the stomach, duodenum, ileum, Peyer's patches, jejunum, and colon, and also extraintestinal sites like the lung, spleen, thymus and mesenteric lymph nodes, were obtained from conventionally reared pigs aged 2 wk to 5.5 years. In addition, tissues were also obtained from 10-wk-old specified pathogen- and germ-free pigs. TCRDV1-DV5 transcripts were amplified by RT-PCR after which complementarity-determining region 3 spectratyping was performed. Individual bands were excised from the gels and directly sequenced. The intestinal TCR delta repertoire showed increasing restriction with age and was highly oligoclonal in the adult 2- to 5.5-year-old pigs. In old pigs, we observed a striking compartmentalization. Different TCR delta repertoires were present between the lungs and the intestinal mucosa but also within different parts of the gastrointestinal tract. However, occasionally we observed identical TCR delta transcripts in the intestine and the lungs and shared clones could be detected also along the entire gastrointestinal tract. Thus, subsets of gammadelta T cells are likely to transport immunological information between different compartments of the immune system. Furthermore, these data support the hypothesis that in each mucosal site, different Ags are responsible for selecting and maintaining the gammadelta TCR over time.

Aging↗