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同种异体肿瘤体内刺激后抗原特异性CD8 + T细胞的迁移与激活

Migration and activation of antigen-specific CD8+ T cells upon in vivo stimulation with allogeneic tumor.

作者信息

Kedl R M, Mescher M F

机构信息

The Center for Immunology and the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.

出版信息

J Immunol. 1997 Jul 15;159(2):650-63.

PMID:9218580
Abstract

The response of CD8+ T cells to allogeneic tumor was studied by adoptive transfer of cells from TCR transgenic 2C mice specific for Ld alloantigen. Transferred cells were monitored during the course of a response to i.p. challenge with live P815 (H-2d) using the 1B2 mAb specific for the 2C TCR. Tumor was present in the draining LN and spleen within 3 to 4 days of challenge. The first changes in 1B2+ cells occurred in the spleen on day 4; VLA-4 expression increased in an Ag-specific manner and L-selectin expression decreased in an Ag-nonspecific manner. The number of 1B2+ cells in the spleen declined over days 4 to 6. The first detectable increase in CD25 expression and blast transformation was in the peritoneal cavity beginning days 5 and 6. Clonal expansion was largely limited to this site and was maximal on day 8. As expansion occurred in the peritoneal cavity; the number of 1B2+ cells in the draining LN and spleen also increased. These cells had an activated phenotype (CD44(high), VLA-4(high)) but most did not express CD25 and were not blasts. These results suggest that initial Ag recognition in the spleen results in altered expression of adhesion receptors so that cells gain access to the peritoneal cavity where they undergo clonal expansion and differentiation. Following the response, 1B2+ cells decline in number but a memory population (CD44(high), L-selectin(high and low)) persists for long times in the spleen and LN.

摘要

通过移植来自对Ld同种异体抗原具有特异性的TCR转基因2C小鼠的细胞,研究了CD8 + T细胞对同种异体肿瘤的反应。在用针对2C TCR的1B2单克隆抗体对活的P815(H-2d)进行腹腔攻击的反应过程中,对转移的细胞进行监测。攻击后3至4天,引流淋巴结和脾脏中出现肿瘤。1B2 +细胞的首次变化发生在第4天的脾脏中;VLA-4表达以抗原特异性方式增加,而L-选择素表达以抗原非特异性方式降低。脾脏中1B2 +细胞的数量在第4至6天下降。CD25表达和母细胞转化的首次可检测到的增加始于第5天和第6天的腹腔。克隆扩增主要限于该部位,在第8天达到最大值。随着腹腔内发生扩增,引流淋巴结和脾脏中1B2 +细胞的数量也增加。这些细胞具有活化的表型(CD44(高),VLA-4(高)),但大多数不表达CD25且不是母细胞。这些结果表明,脾脏中的初始抗原识别导致黏附受体表达改变,从而使细胞进入腹腔,在那里它们经历克隆扩增和分化。反应后,1B2 +细胞数量下降,但记忆群体(CD44(高),L-选择素(高和低))在脾脏和淋巴结中长时间持续存在。

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