Effector function-deficient memory CD8+ T cells clonally expand in the liver and give rise to peripheral memory CD8+ T cells

• Main Authors: Yu-Chia Su, 蘇裕家
• Other Authors: John T. Kung
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/71576250925044167762

博士 === 國立臺灣大學 === 免疫學研究所 === 99 === Upon adoptive transfer into congenic histocompatible hosts, naïve CD8+ T cells stimulated ex vivo by TCR in the presence of IL-4 persist in the hosts and become long-lived memory cells. A unique subset of memory CD8+ T cells resides in the liver (TLM) and this subset is highly reduced in the IL-15Ralpha-knockout (ko) liver. TLM cells are similar to effector memory (TEM) cells in that they are both CD62LlowCCR7-, but are unlike TEM cells in that they express reduced IFN-gamma inducibility, cytolytic activity and TCR-induced proliferation. CFSE dilution assay results indicate that TLM cells undergo IL-15Ralpha-dependent proliferation. Immunofluorescent staining revealed that the TLM cells form a large number of cell clusters in the liver of WT but not IL-15Ralpha-ko mice. TLM cells form clusters through clonal expansion because adoptive transfer of an admixture of TCR+ IL-4-activated Vbeta8+ and Vbeta5+ CD8+ T cells results in clusters composed exclusively of Vbeta5+ or Vbeta8+ cells. Clonal expansion of CD8+ T cells is also found in the liver of Listeria monocytogenes-immune mice. TLM cell clusters in the liver are located around the sinusoid, closely associate with hepatic stellate cells, and are in close association with IL-15+ and IL-15Ralpha+ dendrite-like processes. Sorted CD62Llow TLM cells can migrate to other organs after re-transfer and display increased CD62L expression and become phenotypically similar to central memory (TCM) cells. Our results bring to light a previously unappreciated role of the liver in the growth and maintenance of memory CD8+ T cells. These results also indicate that clonal growth of memory CD8+ T cells in the liver is a normal physiological process and that caution should be exercised in interpreting focal lymphoid growth in clinical liver biopsy specimens as pathology and not normal physiology.