Preferential accumulation of CD103(+) T cells in human livers; its association with extrathymic T cells
ABSTRACT CD103, a mucosal integrin alphaEbeta7, binds to E-cadherin expressed on hepatocytes and bile duct epithelium in the liver. Although CD103+ T cells are enriched in intestinal intraepithelial lymphocytes, the localization of those cells in the liver is unknown.
We investigated whether CD103+ cells are present in human livers, and how they are associated with the intrahepatic development of T cells by flow cytometry and immunohistochemistry.
Human livers contain significantly (P<0.001) higher percentages of CD103+ cells in CD4+ and CD8+ T cells (25.7+/-13.5 and 27.1+/-19.3%, respectively) than peripheral blood lymphocytes. Moreover, CD103+ cells in the liver, but not in peripheral blood, contained T cells with intermediate expression level of T cell receptor alphabeta. Those cells consist of mostly CD4+ and CD4-CD8- cells, and expressed low level of CD56 and interleukin-2 receptor beta chain in most of the population. These characteristics are distinct from natural killer T cells, which have been thought to be extrathymic T cells in human livers. Moreover, intrahepatic CD103+ cells expressed mRNA for recombination-activating gene-1, -2 and pre T cell receptor-alpha detected by reverse transcription-polymerase chain reaction.
CD103+ T cells are preferentially accumulated in human livers, and those T cells show characteristics of extrathymic T cells.
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ABSTRACT: Normal adult human liver (AHL) contains populations of unconventional lymphocytes that have been shown in the mouse to mature locally. The presence of lymphoid progenitors together with IL-7, recombinase-activating gene, and pre-TCR-alpha expression in AHL suggests similar local T cell development activity in humans. Flow cytometry was used to characterize potentially naive hepatic alphabeta-T cells. We looked for evidence of TCR-alphabeta cell development in AHL by quantifying delta deletion TCR excision circles (TRECs) in CD3(pos) populations isolated from the liver and matched blood of eight individuals. Phenotypic analysis of hepatic T cells suggests the presence of Ag-inexperienced populations. TRECs were detected in all blood samples (mean, 164.10 TRECs/ micro g DNA), whereas only two hepatic samples were positive at low levels (59.40 and 1.92). The relatively high level of CD8(pos) T cells in these livers with a naive phenotype suggests that in addition to its role as a graveyard for Ag-specific activated CD8(pos) T cells, naive CD8(pos) T cells may enter the liver without prior activation. The almost complete absence of TRECs suggests that normal AHL is not a site for the development of conventional alphabeta T cells.The Journal of Immunology 06/2004; 172(10):5980-5. DOI:10.4049/jimmunol.172.10.5980 · 5.36 Impact Factor
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ABSTRACT: The characterization of antiviral CTL responses has largely been limited to assessing Ag-specific immune responses in the peripheral blood. Consequently, there is an incomplete understanding of the cellular immune responses at mucosal sites where many viruses enter and initially replicate and how the Ag specificity and activation status of CTL derived from these mucosal sites may differ from that of blood-derived CTL. In this study, we show that EBV-specific CTL responses in the tonsils are of comparable specificity and breadth but of a significantly higher magnitude compared with responses in the peripheral blood. EBV-specific, tonsil-resident, but not PBMC-derived, T cells expressed the integrin/activation marker CD103 (alphaEbeta7), consistent with the detection of its ligand, E-cadherin, on tonsillar squamous cells. These CD8-positive, CD103-positive, tonsil-derived CTL were largely CCR7- and CD45RA- negative effector-memory cells and responded to lower Ag concentrations in in vitro assays than their CD103-negative PBMC-derived counterparts. Thus, EBV-specific CTL in the tonsil, a crucial site for EBV entry and replication, are of greater magnitude and phenotypically distinct from CTL in the peripheral blood and may be important for effective control of this orally transmitted virus.The Journal of Immunology 11/2005; 175(7):4355-62. DOI:10.4049/jimmunol.175.7.4355 · 5.36 Impact Factor