CD4+CD25+ regulatory cells from human peripheral blood express very high levels of CD25 ex vivo.
CD4+CD25+ regulatory cells from human peripheral blood express very high levels of CD25 ex vivo.
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DOI：
10.1002/0470871628.ch6
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发表时间：
2003
影响因子：
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通讯作者：
C. Baecher-Allan;Julia A. Brown;G. Freeman;D. Hafler
中科院分区：
文献类型：
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作者：
C. Baecher-Allan;Julia A. Brown;G. Freeman;D. Hafler
FACS只选择性地分离那些CD25表达水平最高的CD4+T细胞，结果是由功能活性和多种表面抗原的表达定义的高度均一的调节群体。因此，在没有CD45RA表达的情况下，超过98%的CD4+CD25High细胞表达CD45RO。在TCR刺激下，CD4+CD25High细胞是无能和耐受性的，因为它们以接触依赖的方式抑制激活的CD4+CD25反应T细胞的增殖和细胞因子的分泌。相比之下，表达CD25水平较低的CD4+细胞在CD45RO、HLA-DR和CD122表达水平上的异质性更强，并且没有表现出无能或抑制特性。给予CD28共刺激或IL2以最大限度地抗CD3刺激，可适度诱导增殖，并失去可观察到的由CD4+CD25高调节细胞抑制的作用。与CTLA4阻断不同，阻断PD-1与其配体PD-L1的相互作用会影响抑制水平。然而，由于αPD-L1抑制的减少可以通过增加共培养实验中CD4+CD25High T细胞的数量来克服，因此在没有PD-1/PD-L1相互作用的情况下，CD4-CD25高调节的机制可以继续进行，尽管它不是那么有效。
Selective isolation of only those CD4+ T cells that display the highest levels of CD25 by FACS results in a highly homogeneous regulatory population as defined by functional activity and the expression of multiple surface antigens. Thus greater than 98% of CD4+CD25high cells express CD45RO in the absence of CD45RA expression. Upon TCR stimulation CD4+CD25high cells are both anergic and tolerogenic as they inhibit proliferation and cytokine secretion by activated CD4+CD25- responder T cells in a contact-dependent manner. In contrast, CD4+ cells that express lower levels of CD25 are more heterogeneous in their levels of expression of CD45RO, HLA-DR and CD122, and do not exhibit anergic or suppressive characteristics. Providing either CD28 co-stimulation or IL2 to a maximal anti-CD3 stimulus results in a modest induction of proliferation and the loss of observable suppression by CD4+CD25high regulatory cells. Unlike CTLA4 blockade, blocking the interaction of PD-1 with its ligand PD-L1 affects the level of suppression. However, since this reduction in suppression by alphaPD-L1 can be overcome by increasing the number of CD4+CD25high T cells in the co-culture assay, the mechanism of CD4-CD25high regulation can proceed in the absence of PD-1/PD-L1 interactions, although it is not as efficient.