Memory phenotype of CD8+ T cells in MHC class Ia-deficient mice

Memory phenotype of CD8+ T cells in MHC class Ia-deficient mice
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DOI:
10.4049/jimmunol.170.11.5414
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发表时间:
2003-06-01
影响因子:
4.4
通讯作者:
Forman, J
Forman, J
中科院分区:
医学2区
文献类型:
--
作者:
Kurepa, Z;Su, J;Forman, J

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B6.Kb-Db-小鼠缺乏Ia类,但表达正常水平的Ib类分子。它们在胸腺和外周T细胞区室中具有低水平的CD 8 T细胞。虽然这些动物脾脏中CD 8 α α T细胞的百分比增加,但类似于90%的CD 8 T细胞是CD 8 α。与B6动物相反,这些小鼠的大多数CD 8 T细胞具有记忆表型(CD 44(高)CD 122(高)CD 62(低)),包括CD 8 α和CD 8 α α亚群。在B6. K B(-)D(B-)动物的胸腺中,SP CD 8 T细胞的百分比降低,尽管大多数是CD 44(低),与B6小鼠中观察到的相似。来自1天龄B6和B6.Kb-Db-小鼠的脾脏具有相对高比例的CD 44(高)CD 62 L(低)CD 8 T细胞。然而,到第28天,B6小鼠中的大多数CD 8 T细胞具有幼稚表型,而在B6.Kb-Db-小鼠中,记忆表型仍然存在。与在B6动物中发现的CD 44(高)细胞不同,来自B6.Kb-Db-小鼠的大多数CD 44高细胞在活化后不快速分泌IFN-γ。B6 K(B-)D(B-)小鼠中CD 8 T细胞的缺乏可能部分是由于它们不能进行稳态扩增。与此一致,我们发现,与对Ia类抗原有反应的B6 CD 8 T细胞相比,来自这些动物的CD 8 T细胞在X射线照射的同基因宿主中扩增较差。我们检查了B6 CD 8 T细胞在单和双Ia类基因敲除小鼠中的稳态扩增,并能够估计对Ia类与Ib类分子反应的细胞分数。
B6.Kb-Db- mice are devoid of class Ia but express normal levels of class Ib molecules. They have low levels of CD8 T cells in both the thymus as well as peripheral T cell compartments. Although the percentage of splenic CD8alphaalpha T cells is increased in these animals, similar to90% of CD8 T cells are CD8alphabeta. In contrast to B6 animals, most of the CD8 T cells from these mice have a memory phenotype (CD44(high)CD122(high) CD62(low)) including both CD8alphabeta and CD8alphaalpha subsets. In the thymus of B6.Kb(-)D(b-) animals, there is a decrease in the percentage of SP CD8 T cells, although most are CD44(low), similar to that seen in B6 mice. The spleens from day 1-old B6 and B6.Kb-Db- mice have a relatively high proportion of CD44(high) CD62L(low) CD8 T cells. However, by day 28 most CD8 T cells in B6 mice have a naive phenotype while in B6.Kb-Db- mice the memory phenotype remains. Unlike CD44(high) cells that are found in B6 animals, most CD44 high cells from B6.Kb-Db- mice do not secrete IFN-gamma rapidly upon activation. The paucity of CD8 T cells in B6K(b-)D(b-) mice might be due in part to their inability to undergo homeostatic expansion. Consistent with this, we found that CD8 T cells from these animals expand poorly in X-irradiated syngeneic hosts compared with B6 CD8 T cells that respond to class Ia Ags. We examined homeostatic expansion of B6 CD8 T cells in single as well as double class la knockout mice and were able to estimate the fraction of cells reactive against class Ia vs class Ib molecules.