T‐cell activation in the intestinal mucosa

Abstract

SummaryThe vast majority of peripheral T cells exist as resting lymphocytes until a signal for activation has been received. In response to antigen, this involves ligation of the T cell receptor (TCR) and signal transmission through the CD3 complex, which then initiates a cascade of intracellular events that leads to the expression of genes used in T cell activation. T cell activation also requires soluble mediators in the form of cytokines and chemokines that regulate the process in both positive and negative ways, and costimulatory signals received in conjunction with TCR/CD3 signaling are important in the activation of T cells. Unlike T cells in other peripheral immune compartments, small and large intestinal intraepithelial lymphocytes (IELs) bear some but not all properties of activated T cells, suggesting that they constitute a large population of 'partially-activated' effector cells. Because of that, regulation of the IEL activation process must be held in tight check, yet it must be ready to respond to foreign antigen rapidly and effectively. We discuss how costimulatory molecules may hold the key to controlling IEL activation through a multi-phase process beginning with cells that have already entered into the early stage of activation.

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

“…3A). The high expression of CD69 molecules on MAIT cells is in line with what was reported for intrahepatic (21) and intraepithelial gut lymphocytes (24). Despite their activation phenotype, Liv-MAIT cells were in a nonproliferating state, being almost completely negative for Ki-67 (,1% of MAIT, data not shown), similar to the feature described in B-MAIT cells (16) but in contrast to a large proportion of intrahepatic activated conventional T cells (Fig.…”

“…First, a tight control over MAIT cell responsiveness to Ags is crucial to prevent wanton responses within the liver, yet still allow MAIT cells to respond swiftly and effectively to pathogenic Ags. Indeed, we observed that Liv-MAIT cells expressed markers of T cell activation (CD69, CD38, HLA-DR) but were in a noncycling state and were poorly responsive to TCRmediated stimulation; this may be a "partial activation" state similar to that described in intestinal intraepithelial lymphocytes (24). It is worth mentioning that beyond its use as an early activation marker, CD69 was also associated with inflammatory infiltrates (39), TGF-b1 production (40), and regulation of the Th17 response (41).…”

Cd8 enhancer E8 I and Runx factors regulate CD8α expression in activated CD8 + T cells

“…It has been shown that IEL share characteristics of partially activated lymphocytes (29,30). Thus, it is tempting to speculate that CD8αα expression on E8 I −/− IELs is severely impaired because the cells are at least partially activated, and not because of a distinct mode of Cd8a gene regulation in IELs compared with conventional naive CD8 + T cells.…”

Two-marker protein profile predicts poor prognosis in patients with early rectal cancer

“…We have additionally reported the impact of absence of CD8 þ TILs on local recurrence rates in mismatch repair-proficient colon cancer (Zlobec et al, 2008c). The close proximity of activated cytotoxic T cells to the tumour cells may allow for initiation of an effective antitumour immune response despite the generally immunosuppressive nature of the gut (Montufar-Solis et al, 2007). Furthermore, the presence of intraepithelial TILs likely reflects an active peripheral immune response capable of efficiently eradicating micrometastases and thereby contributing to prolonged patient survival.…”