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.
SourceAvailable from: Toni Darville[Show abstract] [Hide abstract]
ABSTRACT: Chlamydia trachomatis causes sexually transmitted infection and reproductive dysfunction worldwide. Identifying a population of endocervical T-cells to target in vaccine development is likely to enhance efficacy of a vaccine and reduce reproductive tract dysfunction. Endocervical samples were obtained from young women and flow cytometric analysis was used to identify lymphocytes that appeared in the genital tract in response to sexually transmitted bacterial infections caused by C. trachomatis. Increased numbers of α4β7+CLA+ memory T-cells, a unique T-cell phenotype, were found in the endocervix of human female subjects infected with C. trachomatis. A unique population of memory T lymphocytes expressing both α4β7 and CLA gain access to reproductive tract tissues during a sexually transmitted infection with C. trachomatis and should be considered in development of vaccines against sexually transmitted infections.American Journal Of Reproductive Immunology 05/2009; 61(6):446-52. DOI:10.1111/j.1600-0897.2009.00705.x · 3.32 Impact Factor
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ABSTRACT: Immunization with high doses of irradiated sporozoites delivered by the bites of infected mosquitoes has been shown to induce protective responses against malaria, mediated in part by CD8(+) T cells. In contrast, natural transmission involving low exposure to live sporozoite antigen fails to elicit strong immunity. In this review, we examine how irradiated sporozoite immunization breaks the natural host-parasite interaction and induces protective CD8(+) T cells. Upon biting, the malaria-infected mosquitoes deposit parasites in the skin, many of which eventually exit to the bloodstream and infect hepatocytes. However, certain antigens, including the circumsporozoite (CS) protein, remain in the skin and are presented in the draining lymph node. These antigens prime specific CD8(+) T cells, which migrate to the liver where they eliminate parasitized hepatocytes. We discuss the relevance of the different tissue compartments involved in the induction and effector phases of this response, as well as the cellular requirements for priming and memory development of CD8(+) T cells, which include a complete dependence on dendritic cells and a near absolute need for CD4(+) T-cell help. Finally, we discuss the impact of the immunodominant CS protein on this protection and the implications of these findings for vaccine design.Immunological Reviews 11/2008; 225:272-83. DOI:10.1111/j.1600-065X.2008.00671.x · 12.91 Impact Factor