Induction and function of eosinophil intercellular adhesion molecule-1 and HLA-DR.
We have previously established that eosinophils studied ex vivo from the sputum of asthmatics express intercellular adhesion molecule-1 (ICAM-1) and HLA-DR, whereas peripheral blood eosinophils do not express these surface proteins. On incubation of highly purified (greater than 99.5% pure) blood eosinophils from normal subjects with T cell supernatants, eosinophil ICAM-1 was induced in 24 h, whereas HLA-DR was maximally induced within 48 h. Recombinant cytokines that enable eosinophil survival (IL-5, IL-3, and granulocyte macrophage-CSF) were found to be unable to induce ICAM-1 or HLA-DR, even when pooled at concentrations individually required for eosinophil survival. However, synergy between these eosinophil survival factors and TNF (-alpha and -beta) was found mainly responsible for ICAM-1 induction, whereas synergy between IL-3 and IFN-gamma occurred for HLA-DR induction. Culture of eosinophils in the presence of cytokines and cycloheximide prevented expression of ICAM-1 and HLA-DR, showing that de novo eosinophil protein synthesis is occurring. At a functional level we demonstrate that ICAM-1-bearing eosinophils have increased adhesion capacity for autologous T cells. In contrast, HLA-DR-expressing eosinophils mediated Ag-specific proliferation of an autologous HLA-DR-restricted T cell clone that was inhibitable by anti-HLA-DR and anti-ICAM-1 mAb. Since eosinophil-mediated Ag presentation was inhibitable by treatment of eosinophils with glutaraldehyde or chloroquine, this suggests that eosinophils participate in Ag uptake, processing, and presentation and have accessory functions. Thus, through the induction of ICAM-1 and HLA-DR on tissue eosinophils, eosinophils have the capacity to interact with leukocytes and present Ag to T cells.
Swiss Institute of Allergy and Asthma Research (SIAF), Davos-Platz.
T T
TT
Hansel
I J
IJ
De Vries
J M
JM
Carballido
R K
RK
Braun
N
N
Carballido-Perrig
S
S
Rihs
K
K
Blaser
C
C
Walker
D000938:Antigen-Presenting Cells / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D003513:Cycloheximide