Intrahepatic activation of naive CD4+ T cells by liver-resident phagocytic cells

Naive T cell activation is normally restricted to the lymphoid organs, in part because of their limited ability to migrate into the parenchyma of peripheral tissues. The liver vasculature is unique, however, and circulating leukocytes within the hepatic sinusoids have direct access to liver-resident...

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Veröffentlicht in:The Journal of immunology (1950) 2014-09, Vol.193 (5), p.2087-2095
Hauptverfasser: Tay, Szun S, Wong, Yik Chun, Roediger, Ben, Sierro, Frederic, Lu, Bo, McDonald, David M, McGuffog, Claire M, Meyer, Nicholas J, Alexander, Ian E, Parish, Ian A, Heath, William R, Weninger, Wolfgang, Bishop, G Alex, Gamble, Jennifer R, McCaughan, Geoffrey W, Bertolino, Patrick, Bowen, David G
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container_issue 5
container_start_page 2087
container_title The Journal of immunology (1950)
container_volume 193
creator Tay, Szun S
Wong, Yik Chun
Roediger, Ben
Sierro, Frederic
Lu, Bo
McDonald, David M
McGuffog, Claire M
Meyer, Nicholas J
Alexander, Ian E
Parish, Ian A
Heath, William R
Weninger, Wolfgang
Bishop, G Alex
Gamble, Jennifer R
McCaughan, Geoffrey W
Bertolino, Patrick
Bowen, David G
description Naive T cell activation is normally restricted to the lymphoid organs, in part because of their limited ability to migrate into the parenchyma 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.
doi_str_mv 10.4049/jimmunol.1400037
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subjects Animals
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
Autoimmune Diseases - pathology
Bone Density Conservation Agents - pharmacology
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - pathology
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - pathology
Clodronic Acid - pharmacology
Kupffer Cells - immunology
Kupffer Cells - pathology
Liposomes
Liver - immunology
Liver - pathology
Liver Diseases - genetics
Liver Diseases - immunology
Liver Diseases - pathology
Lymphocyte Activation
Mice
Mice, Transgenic
title Intrahepatic activation of naive CD4+ T cells by liver-resident phagocytic cells
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