Canine CD4+ CD8+ double-positive T cells can develop from CD4+ and CD8+ T cells
Canine CD4+ CD8+ double-positive T cells can develop from CD4+ and CD8+ T cells
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DOI：
10.1016/j.vetimm.2014.09.008
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发表时间：
2014-12-15
影响因子：
1.8
通讯作者：
von Buttlar, Heiner
中科院分区：
文献类型：
--
作者：
Bismarck, Doris;Moore, Peter F.;von Buttlar, Heiner
长期以来，外周血T细胞上CD 4和CD 8受体的表达被认为是相互排斥的。然而，在犬外周血中，与其他物种如猪或人类似，存在成熟的CD 4（+）CD 8（+）双阳性（dp）T细胞，其同时表达两种表面受体并具有活化T细胞的特征。犬CD 4（+）CD 8（+）dp T细胞是异质性的，并且可以根据其CD 4和CD 8 α表达的强度分为三个亚群：CD 4（亮）CD 8 α（亮）、CD 4（暗）CD 8 α（亮）和CD 4（暗）CD α（暗）。体外刺激犬外周血单个核细胞（PBMC）后，CD 4（+）CD 8 α（+）dp T细胞数量增加，这引起了对其祖细胞的疑问。因此，我们研究的目的是表征犬CD 4（+）CD 8 α（+）dp T细胞的祖细胞。通过细胞示踪实验，我们鉴定了CD 4（+）单阳性（sp）和CD 8 α（+）sp T细胞作为体外刺激后犬CD 4（+）CD 8 α（+）dp T细胞的祖细胞。CD 4（+）sp T细胞几乎只上调CD 8 α α同源二聚体，而CD 8 α（+）sp T细胞可以变成CD 4（+）CD 8 α β（+）或CD 4（+）CD 8 α α（+）。即使在没有其他细胞的情况下，高度纯化的CD 4（+）sp T细胞在体外刺激时也可以变成双阳性，而高度纯化的CD 8 α（+）sp T细胞不能这样做。然而，当在CD 4（-）CD 8 α（-）双阴性（dn）细胞存在下刺激时，CD 8 α（+）sp T细胞可以额外表达CD 4，或者当在CD 4（+）sp T细胞存在下刺激时，CD 8 α（+）sp T细胞可以更有效地表达CD 4。由CD 4（+）sp T细胞分泌的可溶性因子足以上调CD 8 α（+）sp T细胞上的CD 4，但CD 4（+）sp和CD 8 α（+）sp T细胞之间的直接细胞-细胞接触更有效。mRNA分析显示，CD 8 α（+）sp T细胞上额外的CD 4表达来自于de nova合成。因此，可溶性CD 4的摄取或胞啃不太可能是犬双阳性T细胞产生的机制。CD 4（+）CD 8 α（+）dp T细胞高度活化，与其来源无关，除非在CD 8 α（+）sp T细胞与CD 4（-）CD 8 α（-）dn细胞共培养中产生。总体而言，在犬中，与CD 8 α（+）sp T细胞相比，CD 4（+）sp T细胞是CD 4（+）CD 8 α（+）dp T细胞更有效的祖细胞。(C)2014爱思唯尔有限公司版权所有。
For a long time the expression of the CD4 and CD8 receptor on peripheral blood T cells was thought to be mutually exclusive. However, in canine peripheral blood, similar to other species as swine or human for example, mature CD4(+)CD8(+) double-positive (dp) T cells exist which simultaneously express both surface receptors and have features of activated T cells. Canine CD4(+)CD8(+)dp T cells are heterogeneous and can be divided into three subpopulations by their intensity of CD4 and CD8 alpha expression: CD4(bright) CD8 alpha(bright), CD4(dim)CD8 alpha(bright) and CD4(dim)CD alpha(dim). The number of CD4(+)CD8 alpha(+)dp T cells increases after in vitro stimulation of canine peripheral blood mononuclear cells (PBMC) raising the question of their progenitor(s). Thus, the aim of our study was to characterize the progenitor(s) of canine CD4(+)CD8 alpha(+)dp T cells. By cell tracing experiments we identified both CD4(+) single-positive (sp) and also CD8 alpha(+)sp T cells as progenitors of canine CD4(+)CD8 alpha(+)dp T cells after in vitro stimulation. CD4(+)sp T cells almost exclusively upregulate a CD8 alpha alpha homodimer, whereas CD8 alpha(+)sp T cells can become CD4(+)CD8 alpha beta(+) or CD4(+)CD8 alpha alpha(+). Even in the absence of other cells, highly purified CD4(+)sp T cells can become double-positive upon in vitro stimulation, whereas highly purified CD8 alpha(+)sp T cells fail to do so. However, CD8 alpha(+)sp T cells can additionally express CD4 when stimulated in the presence of CD4(-)CD8 alpha(-) double-negative (dn) cells or more efficiently when stimulated in the presence of CD4(+)sp T cells. Soluble factors secreted by CD4(+)sp T cells are sufficient for the upregulation of CD4 on CD8 alpha(+)sp T cells, but direct cell-cell contact between CD4(+)sp and CD8 alpha(+)sp T cells is more efficient. mRNA analysis shows that additional CD4 expression on CD8 alpha(+)sp T cells results from de nova synthesis. Thus, uptake of soluble CD4 or trogocytosis is less likely as mechanism for generation of canine double-positive T cells. CD4(+)CD8 alpha(+)dp T cells are highly activated independent of their origin except when generated in coculture of CD8 alpha(+)sp T cells with CD4(-)CD8 alpha(-)dn cells. Overall, in dog, CD4(+)sp T cells are the more potent progenitors of CD4(+)CD8 alpha(+)dp T cells compared to CD8 alpha(+)sp T cells. (C) 2014 Elsevier B.V. All rights reserved.