Bertolino P, Bowen D G, McCaughan G W, Fazekas de St Groth B
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Australia.
J Immunol. 2001 May 1;166(9):5430-8. doi: 10.4049/jimmunol.166.9.5430.
It is generally accepted that naive T cells recirculate via the blood and lymph, but do not enter nonlymphoid tissues without prior activation and differentiation. In this study, we demonstrate that the liver is an exception to this rule. Naive Des-TCR transgenic CD8(+) T cells specific for H-2K(b) were selectively retained in the liver within a few minutes of adoptive transfer into transgenic Met-K(b) mice expressing H-2K(b) in the liver. Activated CD8(+) cells were found in the liver, but not the blood, as soon as 2 h after transfer and underwent cell division and started to recirculate within 24 h of transfer. In contrast, CD8(+) cells activated in the lymph nodes remained sequestered at that site for 2 days before entering the blood. Our results therefore suggest that, in addition to its previously described role as a non Ag-specific activated T cell graveyard, the liver is involved in Ag-specific activation of naive recirculating CD8(+) T cells. This particular property of the liver, combined with the previously demonstrated ability of hepatocytes to induce tolerance by means of premature CD8(+) T cell death, may be a major mechanism contributing to the acceptance of liver allografts and the chronicity of viral hepatitis.
一般认为，初始T细胞通过血液和淋巴进行再循环，但在未预先激活和分化的情况下不会进入非淋巴组织。在本研究中，我们证明肝脏是这一规则的例外。将对H-2K(b)特异的初始Des-TCR转基因CD8(+) T细胞过继转移到在肝脏中表达H-2K(b)的转基因Met-K(b)小鼠体内后，几分钟内这些细胞就被选择性地保留在肝脏中。转移后2小时，在肝脏中就发现了活化的CD8(+)细胞，但血液中未发现，并且这些细胞在转移后24小时内进行细胞分裂并开始再循环。相比之下，在淋巴结中活化的CD8(+)细胞在进入血液之前会在该部位滞留2天。因此，我们的结果表明，除了其先前被描述为非抗原特异性活化T细胞的墓地的作用外，肝脏还参与初始再循环CD8(+) T细胞的抗原特异性活化。肝脏的这一特殊特性，与先前证明的肝细胞通过过早的CD8(+) T细胞死亡诱导耐受的能力相结合，可能是有助于肝脏同种异体移植的接受和病毒性肝炎慢性化的主要机制。
