Functional responses of resident human T cells in intact liver tissue

[Display omitted] •Resident T cells survive in human liver tissue up to 7 days.•Such T cells are enriched for CD8+, for CD45RO+ and for tissue resident memory cells.•The cells may be activated in their tissue context using a low concentration of anti-CD3.•Such liver T cells rapidly synthesize IFN-gamma, TNF-alpha and IL-2.•After activation, liver T cells express receptors for off-signals. The liver contains a rich mix of T cells, including activated T cells, tissue-resident memory T cells and cells undergoing apoptosis. When antigens are presented in this milieu the default result is functional tolerance. T cell tolerance in the liver could be constitutive, or it could be adaptive, in which case liver cells would become unresponsive after encountering antigen in the liver context. To test this model, we evaluated the potential of human liver T cells to respond to T cell receptor ligation in liver tissue slice cultures. These T cells contained an actively motile subset of CD4+ T cells marked by CCR7 and CD62L, and fully functional subsets of CD4+ and CD8+ T cells that synthesized effector cytokines but subsequently assumed an exhausted phenotype. These data favor the model that human liver T cells are not constitutively tolerant but undergo adaptive tolerance after activation.