Regulatory role of CD8⁺ T lymphocytes in bone marrow eosinophilopoiesis

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 over expressing 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 intrica tely involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice.