TLR-4 regulates CD8+ T cell trapping in the liver.
Mammalian TLRs are understood primarily as an activating system for innate and adaptive immunity, but have also been implicated in sensing cellular damage and in promoting intestinal integrity. In this study we show that TLR-4 also controls the in vivo distribution of activated CD8+ T cells. The liver is a site for trapping and apoptosis of activated CD8+ T cells during systemic immune responses, but the reason for this is unknown. In this study we tested the hypothesis that the liver's constant exposure to endotoxin, derived from commensal bacteria in the gut, acts via TLR-4 to promote activated T cell adhesion. In the absence of TLR-4, the liver was compromised in its ability to sequester activated CD8+ T cells, and there was an inverse correlation between the frequency of activated CD8+ T cells trapped in the liver and their frequency in the circulating pool. Thus, in the absence of any inflammation, TLR-4 ligands play a significant role in the ability of the liver to trap activated CD8+ T cells. This provides a new perspective on the regulation of immune responses by TLR-4 under basal conditions.
John
Beena
B
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Sciences, University of Rochester Medical Center, Rochester, NY 14642, USA. beena_john@urmc.rochester.edu
Crispe
Ian Nicholas
IN
D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018089:Superantigens / Q000494:pharmacology; D051197:Toll-Like Receptor 4
D000956:Antigens, Viral; D008562:Membrane Glycoproteins; C095378:Mtv-7 superantigen, Mouse mammary tumor virus; D011971:Receptors, Immunologic; D018089:Superantigens; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma