CD4+CD25int T cells in inflammatory diseases refractory to treatment with Glucocorticoids
CD4+CD25int T cells in inflammatory diseases refractory to treatment with Glucocorticoids
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DOI：
10.4049/jimmunol.179.11.7941
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Dayan, Colin M.
中科院分区：
文献类型：
--
作者：
Lee, Richard W. J.;Creed, Thomas J.;Dayan, Colin M.
高达30%的自身免疫性、过敏性和淋巴组织增生性疾病患者对糖皮质激素治疗无效。本研究旨在研究这种类固醇抵抗（SR）是否仅限于CD 4（+）T细胞亚群，以及由于IL-2是SR的假定驱动因素，T细胞SR是否与CD 25表达相关。我们发现，SR患者具有一个特征性的活化CD 4（+）T细胞亚群，尽管暴露于高剂量地塞米松（Dex），该亚群仍继续增殖，证明CD 4（+）CD 25（-）细胞对Dex非常敏感，而CD 4（+）CD 25（int）细胞高度SR，并且进一步发现，与单独的每种试剂相比，抗CD 25 mAb与Dex的组合增强了对T细胞增殖的抑制。因此，我们得出结论，SR是不是所有淋巴细胞的一般属性，但驻留在T细胞亚群，这是普遍存在于SR患者和表达中间水平的CD 25。因此，我们提出了一个新的范式SR疾病，其中糖皮质激素治疗积极选择SR细胞，产生一个群体的耐药淋巴细胞，使持续的炎症。
Up to 30% of patients with autoimmune, allergic, and lymphoproliferative diseases are refractory to glucocorticoid therapy. The present study was undertaken to investigate whether such steroid resistance (SR) is limited to a subpopulation of CD4(+) T cells and, as IL-2 is a putative driver of SR, whether T cell SR is associated with CD25 expression. We show that SR patients have a characteristic subgroup of activated CD4(+) T cells that continue to proliferate despite exposure to high-dose Dexamethasone (Dex), demonstrate that CD4(+)CD25(-) cells are exquisitely sensitive to Dex whereas CD4(+)CD25(int) cells are highly SR, and further find that the combination of an anti-CD25 mAb with Dex enhances suppression of T cell proliferation compared with each agent alone. We therefore conclude that SR is not a general property of all lymphocytes but resides in T cell subpopulations, which are prevalent in SR patients and express intermediary levels of CD25. As a result, we propose a new paradigm for SR disease in which glueocorticoid therapy positively selects SR cells, generating a population of drug-resistant lymphocytes that perpetuate on-going inflammation.