Laouar A, et al 2005

Laouar A, et al 2005

The intestinal mucosal immune system, one that serves a critical role in response to invading pathogens yet suppressed responses to resident commensal flora, is functionally different from the immune system of secondary lymphoid organs. T cells in the gut have expression of different adhesion molecules, have a constitutively active phenotype, variations on signal transduction pathways and many more differences compared to the peripheral T cells.

Furthermore, the antigen presenting cells (APCs) in the mucosa are unique. The DC cells in the gut elicit T cell secretion of IL-10 while those T cells stimulated by DC cells from the spleen secrete IFN-gamma. These differences may point to the differences in the local immune response to antigen since IL-10 is involved in the downregulation of TH1 cytokines.

These authors aim to understand how mucosal T cells are activated and which APCs are responsible for the regulation of these processes. They found a unique population of APCs that occur exclusively in the lamina propria and constitutively express CD70, a TNF-related costimulatory ligand typically transiently expressed.

Since these cells had an unusual expression of CD70, the authors aimed to find the origin of these cells. They lacked expression of CD45 and weakly stained for B220. Using a bone marrow reconstitution assay, they found that these cells had a nonhematopoietic origin. The exact lineage remains to be determined.

CD70 interaction with CD27 is critical for stimulation of T cell proliferation. The authors used anti-CD70 to block normal interaction of CD70 with CD27 in these cells and found that it could block the T cell proliferation in their assay. The authors then stimulated the T cells with epitopes for a CD8+ and CD4+ T cell response and measured IFN-g. The results indicate that CD70+ APCs can stimulate CD8+ and CD4+ T cells in the gut.

The author’s results suggest that strong costimulation provided by CD70+ APCs may be necessary to activate T cells in the generally suppressive intestinal milieu. Furthermore the authors state that their findings may also provide a tool for augmenting the mucosal response to an oral vaccine or for interfering with excessive mucosal immune response in situations such as inflammatory bowel disease.


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