Regulation of allergen-induced bone marrow eosinophilopoiesis: role of CD4+ and CD8+ T cells.
BACKGROUND
The mechanisms of the distant stimulation of the bone marrow (BM) after airway allergen exposure remain largely obscure. T cells have been implicated in allergic airway inflammation but their role in allergen-induced BM eosinophilopoiesis is poorly understood. The aim of this study was to determine the role of CD4(+) and CD8(+) T cells in allergen-induced BM eosinophilopoiesis.


METHODS
Ovalbumin (OVA)-sensitized wild type (WT), CD4 knockout (CD4-/-) and CD8 knockout (CD8-/-) mice were exposed intranasally to OVA or saline. Bromo-deoxyuridine (BrdU) was used to label newly produced cells. Bone marrow, blood and bronchoalveolar lavage (BAL) were sampled 24 h after the final exposure. Immunostaining for newly produced eosinophils (i.e. BrdU(+)/MBP(+)) and BM eosinophil progenitor [CD34(+)/CD45(+)/interleukin-5 (IL-5)Ralpha(+)] cells was performed.


RESULTS
The number of newly produced BM eosinophils (BrdU(+)/MBP(+) cells) was significantly reduced in allergen exposed CD4-/- or CD8-/- mice compared with allergen exposed WT mice, which was followed by a subsequent decrease in newly produced blood and airway eosinophils. Furthermore, BM eosinophil progenitors were significantly reduced in allergen exposed CD4-/- and CD8-/- mice compared with WT mice. Finally, serum IL-5 and Bronchoalveolar lavage fluid eotaxin-2 levels were abolished in allergen exposed CD4-/- mice to levels seen in saline exposed WT mice.


CONCLUSIONS
These data suggests that both CD4(+) and CD8(+) T cells have a regulatory role in allergen-induced BM eosinophilopoiesis, whereas CD4(+) T cells are obligatory for allergen-induced airway eosinophilia. The subsequent traffic of eosinophils to the airways is likely to be at least partly regulated by a CD4(+) T-cell-dependent local airway eotaxin-2 production.
Rådinger
M
M
Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden.
Bossios
A
A
Alm
A-S
AS
Jeurink
P
P
Lu
Y
Y
Malmhäll
C
C
Sjöstrand
M
M
Lötvall
J
J
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054423:Chemokine CCL24 / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019891:Leukopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*
D000485:Allergens; D018952:Antigens, CD34; D015704:CD4 Antigens; D016827:CD8 Antigens; D054423:Chemokine CCL24; D010047:Ovalbumin; D017493:Leukocyte Common Antigens