Blocking intrahepatic deletion of activated CD8+ T cells by an altered peptide ligand.
BACKGROUND
Activated CD8(+) T cells are retained by the healthy liver where the majority undergo apoptosis. The intrahepatic apoptosis of activated CD8(+) T cells is enhanced by the presence of SIINFEKL peptide. It is of great interest to identify strategies for maintaining intrahepatic T cell number and function in the presence of SIINFEKL peptides.


OBJECTIVE
Our aim was to test if low affinity peptides can block SIINFEKL peptide induced T cell deletion.


METHODS
We used an in vivo model of intrahepatic CD8(+) T cell deletion with peptides of different affinities.


CONCLUSIONS
We show that the intrahepatic deletion of CD8(+) T cells by SIINFEKL peptide results in loss of in vivo cytotoxic T lymphocyte function. In contrast we show that a low affinity peptide (G4) does not result in intrahepatic deletion of CD8(+) T cells. High concentrations G4 peptide can however block intrahepatic deletion of activated CD8(+) T cells, and prevent loss of in vivo cytotoxicity due to SIINFEKL peptide. This is the first demonstration of blocking of SIINFEKL peptide induced CD8(+) T cell deletion in the liver, with enhancement of in vivo cytotoxicity.
Kuniyasu
Yuhshi
Y
Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520 8019, USA.
Qamar
Amir
A
Sheikh
Shehzad Zafar
SZ
Jhandier
Muhammad Nauman
MN
Hakim
Wyel
W
Mehal
Wajahat Zafar
WZ
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D004527:Egg Proteins / Q000494:pharmacology*; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000494:pharmacology*; D010446:Peptide Fragments; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D004527:Egg Proteins; D008024:Ligands; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin