Extra-Thymic Physiological T Lineage Progenitor Activity Is Exclusively Confined to Cells Expressing either CD127, CD90, or High Levels of CD117

T cell development depends on continuous recruitment of progenitors from bone marrow (BM) to the thymus via peripheral blood. However, both phenotype and functional characteristics of physiological T cell precursors remain ill-defined. Here, we characterized a putative CD135+CD27+ T cell progenitor population, which lacked expression of CD127, CD90, and high levels of CD117 and was therefore termed triple negative precursor (TNP). TNPs were present in both BM and blood and displayed robust T lineage potential, but virtually no myeloid or B lineage potential, in vitro. However, TNPs did not efficiently generate T lineage progeny after intravenous or intrathymic transfer, suggesting that a physiological thymic microenvironment does not optimally support T cell differentiation from TNPs. Thus, we propose that physiological T cell precursors are confined to populations expressing either CD127, CD90, or high levels of CD117 in addition to CD135 and CD27 and that TNPs may have other physiological functions

High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability

High-level microsatellite instability (MSI-H) in colorectal cancer accounts for about 12% of colorectal cancers and is typically associated with a dense infiltration with cytotoxic CD8-positive lymphocytes. The role of regulatory T cells that may interfere with the host's antitumoural immune response in MSI-H colorectal cancers has not been analysed yet. Using an antibody directed against the regulatory T-cell marker transcription factor forkhead box P3 (FOXP3), regulatory T cells were examined in 70 colorectal cancers with known MSI status (MSI-H, n=37; microsatellite stable, n=33). In MSI-H colorectal cancers, we found a significantly higher intraepithelial infiltration with FOXP3-positive cells (median: 8.5 cells per 0.25 mm2 vs 3.1 cells per 0.25 mm2 in microsatellite stable, P<0.001), and a significantly elevated ratio of intraepithelial to stromal infiltration (0.05 vs 0.01 in microsatellite stable, P<0.001). CD8-positive cell counts were related positively to the number of FOXP3-positive cells (Spearman's ρ=0.56 and 0.55, respectively). Our results show that the elevated number of CD8-positive lymphocytes found in MSI-H colorectal cancers is paralleled by an enhanced infiltration with CD8-negative FOXP3-positive cells. These data suggest that FOXP3-positive cells may play a role in the regulation of the immune response directed against MSI-H colorectal cancers at the primary tumour site