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Repertoire at Mucosal and Extraintestinal Sites: The Pig as a Model for Analyzing the Effects of Age and Microbial Factors1


* Medizinische Klinik II, Division of Gastroenterology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany; and
Center of Anatomy, Medical School of Hannover, Hannover, Germany

T cells are an important component of the mucosal
immune system. Previously, we have shown that the TCR
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,
Peyers 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
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
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
transcripts in the intestine and the lungs and shared
clones could be detected also along the entire gastrointestinal tract.
Thus, subsets of 
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

TCR over time.
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