SFB 1054 Seminar - Roland Ruscher - 12.00 pm

Title: CD8αα+ Intestinal Intraepithelial Lymphocytes (IEL) Arise from Two Thymic Precursors and Seed the Intestine in a Tight Wave in Early Life

TCRαβ+ CD8αα+ intestinal intraepithelial lymphocytes (CD8αα IEL) descend from thymic precursors. To better define this IEL precursor (IELp) population, we analyzed their maturation, localization, and emigration. Using rigorous exclusion criteria, we defined two precursors among DN TCRβ+ thymocytes: a nascent PD-1+ population and a T-bet+ population that accumulates with age. Both gave rise to intestinal CD8αα IEL upon adoptive transfer. In adult mice, PD-1+ cells contained more self-reactive clones, localized to the cortex, and were dominant in S1PR1-dependent thymic egress. Gut homing α4β7 was already expressed by these IELp at a thymic stage. To understand the kinetics of CD8αα IEL seeding the intestine, we performed “time-stamp” experiments: We crossed Cd4CreERT2 with Rosa26TdT (stop-floxed tdTomato) mice. In these mice, tamoxifen or its metabolite 4-OHT permanently labels every CD4 expressing cell. As TCRαβ T cells (including CD8αα IEL) go through a CD4+CD8+ stage during thymic development, a single dose of tamoxifen or 4-OHT will label thymic IEL precursors permanently, so that they can be tracked when seeding the gut. Our results indicate that these cells enter the intestine during a narrow time window in early life and that this influx is almost completely shut down by the age of 3 weeks. These data provide an important foundation for understanding the biology of this abundant population of barrier surface T cells. 

Venue:

BioMedical Center (BMC), Room N 01.017,
Großhaderner Str. 9, Planegg-Martinsried

Host: Ludger Klein (A01)

If you wish to meet with the speaker, please contact Katharina Frank.