Early intrahepatic accumulation of CD8+ T cells provides a source of effectors for nonhepatic immune responses.
Interactions between the liver and CD8+ T cells can lead to tolerance, due in part to CD8+ T cell death. To test whether this was the case in an extrahepatic infection, we investigated the fate and effector capacity of intrahepatic CD8+ T cells during lung-restricted influenza infection in mice. Virus-specific T cells accumulated in livers without detectable intrahepatic presentation of viral Ags, and this accumulation was not restricted to the contraction phase, but was apparent as early as day 5. Intrahepatic influenza-specific cells were functionally similar to those recovered from the bronchioalveolar lavage, based on ex vivo cytokine production and specific target lysis. Both adoptive transfer of liver lymphocytes and orthotopic liver transplant of organs containing accumulated effector T cells revealed that activated CD8s from the liver were viable, expanded during reinfection, and generated a memory population that trafficked to lymphoid organs. Thus, intrahepatic CD8+ T cells re-enter circulation and generate functional memory, indicating that the liver does not uniformly incapacitate activated CD8+ T cells. Instead, it constitutes a substantial reservoir of usable Ag-specific effector CD8+ T cells involved in both acute and recall immune responses.
Polakos
Noelle K
NK
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Klein
Ingo
I
Richter
Martin V
MV
Zaiss
Dietmar M
DM
Giannandrea
Matthew
M
Crispe
Ian N
IN
Topham
David J
DJ
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D002449:Cell Aggregation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D007156:Immunologic Memory; D016130:Immunophenotyping; D053121:Influenza A Virus, H2N2 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007700:Kinetics; D008099:Liver / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016031:Liver Transplantation / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology