Research

Regulatory role of CD8⁺ T lymphocytes in bone marrow eosinophilopoiesis

Madeleine Rådinger^1* , Svetlana Sergejeva^1,2* , Anna-Karin Johansson¹ , Carina Malmhäll¹ , Apostolos Bossios¹ , Margareta Sjöstrand¹ , James J Lee³ and Jan Lötvall¹

¹  Lung Pharmacology Group, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden

²  The Unit for Lung Investigations, Faculty of Science, Department of Gene Technology, Tallinn University of Technology, Estonia

³  Divison of Pulmonary Medicine, Mayo Clinic, Scottsdale, AZ 85259, USA

author email corresponding author email* Contributed equally

Respiratory Research 2006, 7:83doi:10.1186/1465-9921-7-83

Published:	1 June 2006

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; CD3^IL-5+ mice) were bred with gene knockout mice lacking either CD4⁺ T lymphocytes (CD4^-/-) or CD8⁺ T lymphocytes (CD8^-/-) to produce CD3^IL-5+ knockout mice deficient in CD4⁺ T lymphocytes (CD3^IL-5+/CD4^-/-) and CD8⁺ T lymphocytes (CD3^IL-5+/CD8^-/-), respectively. Secondly, CD3⁺, CD4⁺ and CD8⁺ T lymphocytes from naïve CD3^IL-5+ and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3^IL-5+, CD3^IL-5+/CD8^-/- and CD3^IL-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 CD3^IL-5+/CD8^-/- mice compared to CD3^IL-5+ mice and CD3^IL-5+/CD4^-/- mice. Serum IL-5 was significantly higher in CD3^IL-5+/CD4^-/- mice compared to CD3^IL-5+ mice but there was no difference in serum IL-5 between CD3^IL-5+/CD4^-/- and CD3^IL-5+/CD8^-/- mice. Adoptive transfer of CD8⁺, but not CD4⁺ T lymphocytes from naïve CD3^IL-5+ and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3^IL-5+/CD8^-/- mice developed lower numbers of BM eosinophils compared to CD3^IL-5+ mice and CD3^IL-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.