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; 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.


CONCLUSIONS
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.
Rådinger
Madeleine
M
Lung Pharmacology Group, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden. madeleine.radinger@lungall.gu.se
Sergejeva
Svetlana
S
Johansson
Anna-Karin
AK
Malmhäll
Carina
C
Bossios
Apostolos
A
Sjöstrand
Margareta
M
Lee
James J
JJ
Lötvall
Jan
J
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017252:CD3 Complex / Q000032:analysis / Q000235:genetics; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D016827:CD8 Antigens / Q000032:analysis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D047093:Eosinophil Major Basic Protein / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007958:Leukocyte Count; D019891:Leukopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D010047:Ovalbumin; D011657:Pulmonary Eosinophilia / Q000097:blood / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D015848:Interleukin-5; D010047:Ovalbumin; D047093:Eosinophil Major Basic Protein