Premium
Kupffer cells required for high affinity peptide‐induced deletion, not retention, of activated CD8+ T cells by mouse liver
Author(s) -
Kuniyasu Yuhshi,
Marfani Suhail Mohammed,
Inayat Irteza Bin,
Sheikh Shehzad Zafar,
Mehal Wajahat Zafar
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20153
Subject(s) - peptide , cytotoxic t cell , cd8 , microbiology and biotechnology , chemistry , kupffer cell , biology , cancer research , medicine , biochemistry , immunology , immune system , in vitro
Abstract The immune response to foreign antigens in the liver is often suboptimal and this is clinically relevant in chronic persistence of hepatotropic viruses. In chronic infection with the hepatitis C virus, activated CD8+ T cells specific for viral epitopes are present in the peripheral blood and the liver, yet viral clearance is unusual. To define the fate of activated CD8+ entering the liver, we developed a mouse model of portal vein injection of activated CD8+ T cells in vivo . Activated CD8+ T cells are retained very efficiently by the liver and undergo an approximately 8‐fold expansion in the first 48 hours. This expansion is followed by apoptosis and a decline in numbers of the retained cells over the next 4 days. The presence of high affinity (HA) antigen does not affect the initial retention by the liver but greatly limits the expansion in the first 48 hours by increasing apoptosis of the retained cells. In the absence of Kupffer cells, the initial retention and expansion are unchanged, but HA antigen does not limit the expansion of the liver CD8+ T cell pool. In conclusion, these data identify a previously unknown phase of CD8+ T cell expansion after entering the liver, demonstrate that HA antigen limits the hepatic CD8+ T cell pool by inducing apoptosis, and that this effect requires Kupffer cells. Interfering with antigen presentation by Kupffer cells may be a strategy to limit HA antigen‐induced deletion of activated CD8+ T cells entering the liver. (H EPATOLOGY 2004;39;1017–1027.)