1. Regulatory role of CD8+ T lymphocytes in bone marrow eosinophilopoiesis.
- Author
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Rådinger M, Sergejeva S, Johansson AK, Malmhäll C, Bossios A, Sjöstrand M, Lee JJ, and Lötvall J
- Subjects
- Adoptive Transfer, Animals, Bronchoalveolar Lavage Fluid cytology, CD3 Complex analysis, CD3 Complex genetics, CD4 Antigens analysis, CD4 Antigens genetics, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes transplantation, CD8 Antigens analysis, CD8 Antigens genetics, CD8-Positive T-Lymphocytes transplantation, Eosinophil Major Basic Protein biosynthesis, Interleukin-5 biosynthesis, Interleukin-5 blood, Interleukin-5 genetics, Leukocyte Count, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Ovalbumin, Pulmonary Eosinophilia blood, Respiratory Hypersensitivity blood, T-Lymphocyte Subsets transplantation, Bone Marrow Cells immunology, CD8-Positive T-Lymphocytes immunology, Eosinophils immunology, Leukopoiesis, Pulmonary Eosinophilia immunology, Respiratory Hypersensitivity immunology, T-Lymphocyte Subsets immunology
- 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.
- Published
- 2006
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