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Regulatory role of CD8<sup>+ </sup>T lymphocytes in bone marrow eosinophilopoiesis
oleh: Bossios Apostolos, Malmhäll Carina, Johansson Anna-Karin, Sergejeva Svetlana, Rådinger Madeleine, Sjöstrand Margareta, Lee James J, Lötvall Jan
Format: | Article |
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Diterbitkan: | BMC 2006-06-01 |
Deskripsi
<p>Abstract</p> <p>Background</p> <p>There is a growing body of evidence to suggest that CD8<sup>+ </sup>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<sup>+ </sup>T lymphocytes, as well as CD4<sup>+ </sup>T lymphocytes, may be involved in this process.</p> <p>Methods</p> <p>Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3<sup>+ </sup>T lymphocytes (NJ.1638; CD3<sup>IL-5+ </sup>mice) were bred with gene knockout mice lacking either CD4<sup>+ </sup>T lymphocytes (CD4<sup>-/-</sup>) or CD8<sup>+ </sup>T lymphocytes (CD8<sup>-/-</sup>) to produce CD3<sup>IL-5+ </sup>knockout mice deficient in CD4<sup>+ </sup>T lymphocytes (CD3<sup>IL-5+</sup>/CD4<sup>-/-</sup>) and CD8<sup>+ </sup>T lymphocytes (CD3<sup>IL-5+</sup>/CD8<sup>-/-</sup>), respectively. Secondly, CD3<sup>+</sup>, CD4<sup>+ </sup>and CD8<sup>+ </sup>T lymphocytes from naïve CD3<sup>IL-5+ </sup>and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3<sup>IL-5+</sup>, CD3<sup>IL-5+</sup>/CD8<sup>-/- </sup>and CD3<sup>IL-5+</sup>/CD4<sup>-/- </sup>mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments.</p> <p>Results</p> <p>The number of BM eosinophils was significantly reduced in CD3<sup>IL-5+</sup>/CD8<sup>-/- </sup>mice compared to CD3<sup>IL-5+ </sup>mice and CD3<sup>IL-5+</sup>/CD4<sup>-/- </sup>mice. Serum IL-5 was significantly higher in CD3<sup>IL-5+</sup>/CD4<sup>-/- </sup>mice compared to CD3<sup>IL-5+ </sup>mice but there was no difference in serum IL-5 between CD3<sup>IL-5+</sup>/CD4<sup>-/- </sup>and CD3<sup>IL-5+</sup>/CD8<sup>-/- </sup>mice. Adoptive transfer of CD8<sup>+</sup>, but not CD4<sup>+ </sup>T lymphocytes from naïve CD3<sup>IL-5+ </sup>and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3<sup>IL-5+</sup>/CD8<sup>-/- </sup>mice developed lower numbers of BM eosinophils compared to CD3<sup>IL-5+ </sup>mice and CD3<sup>IL-5+</sup>/CD4<sup>-/- </sup>mice.</p> <p>Conclusion</p> <p>This study shows that CD8<sup>+ </sup>T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice.</p>