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 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 naive 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(IL5+)/ 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 naive 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.