Loading...
Please wait, while we are loading the content...
Similar Documents
This information is current as Cells by Liver-Resident Phagocytic Cells T + Intrahepatic Activation of Naive CD 4
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bowen, David Geoffrey Gamble Mccaughan, Geoffrey W. Bertolino, Patrick Heath, R. V. Weninger, Wolfgang J. Bishop, Gail A. Jennifer, Roberts Meyer, Nicholas J. Alexander, Ian E. Parish, Ian A. William Sierro Mcdonald, David M. Mcguffog, Claire Tay, Szun Szun Wong, Yik Chun Roediger, Ben |
| Copyright Year | 2014 |
| Abstract | Naive T cell activation is normally restricted to the lymphoid organs, in part because of their limited ability to migrate into the paren-chyma of peripheral tissues. The liver vasculature is unique, however, and circulating leukocytes within the hepatic sinusoids have direct access to liver-resident cells, which include an abundant population of Kupffer cells. It is well accepted that recognition of cognate Ag within the liver leads to naive CD8 + T cell activation in situ, but it is unclear whether the liver also supports naive CD4 + T cell activation. In this study, we show that naive CD4 + T cells can be activated to proliferate in the liver when cognate Ag expression is induced in hepatocytes by recombinant adeno-associated viral vectors. Ag-specific retention and activation of naive CD4 + T cells within the liver are independent of lymphoid tissues but dependent on a clodronate liposome–sensitive population of liver-resident phagocytic cells. To our knowledge, this study provides the first unequivocal evidence that naive CD4 + T cells can be activated in a nonlymphoid organ. It also gives critical insight into how CD4 + T cells specific for Ag expressed in the liver are recruited to participate in protective or pathological responses during hepatotropic infections and autoimmune liver disease. T he initiation of adaptive immune responses, as well as the development of peripheral tolerance, depend on CD4 + T cell recognition of peptide:MHC class II (pMHC-II) complexes on the surface of APCs. Although several cell types express MHC class II, including B cells and macrophages, it is generally accepted that dendritic cells (DCs) initiate primary activation of peripheral naive CD4 + T cells within secondary lym-phoid organs, such as the lymph nodes (LNs) and spleen (1). This is due, in large part, to the well-documented restriction of naive T cell recirculation to the blood, lymph, and specific areas of lymphoid tissues (2). Thus, naive T cells do not express the requisite adhesion molecules and chemokine receptors required to access macrophages in nonlymphoid organs or the B cell zones within lymphoid organs (3). Several studies from our laboratory and other groups have demonstrated that the liver is an exception to the general rule of T cell trafficking, because it is able to retain and activate naive CD8 + T cells that recognize their cognate Ag in this organ (4–7). This unique property is most likely facilitated by the unique architecture of the … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/early/2014/07/26/jimmunol.1400037.full.pdf |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/193/5/2087.full.pdf?with-ds=yes |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/193/5/2087.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
