Eosinophils promote allergic disease of the lung by regulating CD4(+) Th2 lymphocyte function.
Eosinophils are primarily thought of as terminal effectors of allergic responses and of parasite elimination. However, limited studies suggest a more discrete immunomodulatory role for this leukocyte during these inflammatory responses. In this investigation, we highlight the potential of eosinophils to act as APCs and thus modulators of allergic responses by influencing Th2 cell function. In response to Ag provocation of the allergic lung, eosinophils rapidly trafficked to sites of Ag deposition (airways lumen) and presentation (lung-associated lymph nodes and T cell-rich paracortical zones). Eosinophils from the allergic lung expressed class II MHC peptides, T cell costimulatory molecules (CD80 and CD86), and rapidly internalized and processed Ag that was sampled from within the airway lumen. Ag-loaded eosinophils promoted the production of IL-4, IL-5, and IL-13 in cocultures with in vitro-polarized Th2 cells and induced IL-5 production in a dose-dependent manner from Ag-specific CD4(+) T cells isolated from allergic mice. In addition, Ag-loaded eosinophils primed for Th2 cell-driven allergic disease of the lung when transferred to naive mice. Thus, eosinophils have the potential to not only activate Th2 cells to release disease-modulating cytokines but also to assist in priming the immune system for allergic responses. This investigation highlights the potential of eosinophils to not only act as terminal effector cells but also to actively modulate allergic inflammation by amplifying Th2 cell responses.
MacKenzie
J R
JR
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Mattes
J
J
Dent
L A
LA
Foster
P S
PS
D000280:Administration, Inhalation; D000485:Allergens / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002633:Chemotaxis; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008562:Membrane Glycoproteins; D010047:Ovalbumin