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CD8 + T淋巴细胞在骨髓嗜酸性粒细胞生成中的调节作用。

Regulatory role of CD8+ T lymphocytes in bone marrow eosinophilopoiesis.

作者信息

Rådinger Madeleine, Sergejeva Svetlana, Johansson Anna-Karin, Malmhäll Carina, Bossios Apostolos, Sjöstrand Margareta, Lee James J, Lötvall Jan

机构信息

Lung Pharmacology Group, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden.

出版信息

Respir Res. 2006 Jun 1;7(1):83. doi: 10.1186/1465-9921-7-83.

DOI:10.1186/1465-9921-7-83
PMID:16740158
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1534027/
Abstract

BACKGROUND

There is a growing body of evidence to suggest that CD8+ T lymphocytes contribute to local allergen-induced eosinophilic inflammation. Since bone marrow (BM) responses are intricately involved in the induction of airway eosinophilia, we hypothesized that CD8+ T lymphocytes, as well as CD4+ T lymphocytes, may be involved in this process.

METHODS

Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3+ T lymphocytes (NJ.1638; CD3IL-5+ mice) were bred with gene knockout mice lacking either CD4+ T lymphocytes (CD4-/-) or CD8+ T lymphocytes (CD8-/-) to produce CD3IL-5+ knockout mice deficient in CD4+ T lymphocytes (CD3IL-5+/CD4-/-) and CD8+ T lymphocytes (CD3IL-5+/CD8-/-), respectively. Secondly, CD3+, CD4+ and CD8+ T lymphocytes from naïve CD3IL-5+ and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3IL-5+, CD3IL-5+/CD8-/- and CD3IL-5+/CD4-/- mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments.

RESULTS

The number of BM eosinophils was significantly reduced in CD3IL-5+/CD8-/- mice compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice. Serum IL-5 was significantly higher in CD3IL-5+/CD4-/- mice compared to CD3IL-5+ mice but there was no difference in serum IL-5 between CD3IL-5+/CD4-/- and CD3IL-5+/CD8-/- mice. Adoptive transfer of CD8+, but not CD4+ T lymphocytes from naïve CD3IL-5+ and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3IL-5+/CD8-/- mice developed lower numbers of BM eosinophils compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice.

CONCLUSION

This study shows that CD8+ T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice.

摘要

背景

越来越多的证据表明，CD8 + T淋巴细胞参与局部变应原诱导的嗜酸性粒细胞炎症。由于骨髓（BM）反应复杂地参与气道嗜酸性粒细胞增多的诱导过程，我们推测CD8 + T淋巴细胞以及CD4 + T淋巴细胞可能参与此过程。

方法

采用了几种方法。首先，将在CD3 + T淋巴细胞中过表达白细胞介素-5（IL-5）的小鼠（NJ.1638；CD3IL-5 +小鼠）与缺乏CD4 + T淋巴细胞（CD4 - / -）或CD8 + T淋巴细胞（CD8 - / -）的基因敲除小鼠进行杂交，分别产生缺乏CD4 + T淋巴细胞（CD3IL-5 + / CD4 - / -）和CD8 + T淋巴细胞（CD3IL-5 + / CD8 - / -）的CD3IL-5 +基因敲除小鼠。其次，将来自未致敏的CD3IL-5 +和C57BL / 6小鼠的CD3 +、CD4 +和CD8 + T淋巴细胞过继转移至免疫缺陷的SCID-bg小鼠，以确定它们对骨髓嗜酸性粒细胞增多的影响。第三，对CD3IL-5 +、CD3IL-5 + / CD8 - / -和CD3IL-5 + / CD4 - / -小鼠进行致敏和变应原激发。在所有实验中均采集骨髓和血液样本。

结果

与CD3IL-5 +小鼠和CD3IL-5 + / CD4 - / -小鼠相比，CD3IL-5 + / CD8 - / -小鼠骨髓嗜酸性粒细胞数量显著减少。与CD3IL-5 +小鼠相比，CD3IL-5 + / CD4 - / -小鼠血清IL-5显著升高，但CD3IL-5 + / CD4 - / -和CD3IL-5 + / CD8 - / -小鼠之间血清IL-5无差异。将未致敏的CD3IL-5 +和C57BL / 6小鼠的CD8 +而非CD4 + T淋巴细胞过继转移至免疫缺陷的SCID-bg小鼠可恢复骨髓嗜酸性粒细胞增多。此外，与CD3IL-5 +小鼠和CD3IL-5 + / CD4 - / -小鼠相比，变应原激发的CD3IL-5 + / CD8 - / -小鼠骨髓嗜酸性粒细胞数量较少。

结论

本研究表明，CD8 + T淋巴细胞复杂地参与未致敏以及致敏和变应原激发小鼠的骨髓嗜酸性粒细胞生成的调节。

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