HLA-DR-dependent increased mannan-induced lymphoproliferative response in atopic eczema dermatitis syndrome.
BACKGROUND
In yeast-sensitive atopic eczema dermatitis syndrome (AEDS), yeast mannan induces highly elevated specific IgE levels and lymphoproliferative responses. In healthy individuals the involvement of both human leukocyte antigen (HLA)-dependent T-cell activation and non-HLA-dependent activation, e.g. by crosslinking of the cell surface mannose receptors, has been suggested. In the present study the HLA dependence and the role of crosslinking in the lymphoproliferative response to mannan in AEDS has been analyzed.


METHODS
Twenty patients with AEDS and 12 controls with no history of allergic diseases were included in the study. Mannan from Candida albicans was prepared according to the Cetavlon method. Following isolation using Ficoll-Hypaque, peripheral blood mononuclear cells (PBMC) were incubated with the mannan preparation in the absence and presence of different concentrations of neutralizing anti-HLA antibodies and alpha-methylmannoside for 6 days and proliferative responses were measured by 3H-thymidine incorporation and scintilloradiography.


RESULTS
In AEDS patients with elevated mannan-specific serum IgE, the C. albicans mannan induced lymphoproliferation. Mannan-induced lymphoproliferative responses could be inhibited, dose-dependently, by neutralizing anti-HLA-DR, but not anti-HLA-DQ antibodies in AEDS patients and healthy controls. The addition of alpha-methylmannoside, that blocks binding to mannose receptors, inhibited lymphoproliferative responses in a dose-dependent way by 50% only in healthy controls, but not in AEDS patients. Levels of inhibition of the proliferation by alpha-methylmannoside correlated inversely with the yeast- and mannan-specific IgE levels.


CONCLUSIONS
These results show that in healthy subjects yeast mannan activates lymphocytes both in an HLA-DR-dependent manner and as a result of direct crosslinking of the cell surface. However, in AEDS the elevated lymphoproliferative response is HLA-DR-dependent, although only a slight proportion of this response results from direct crosslinking.
Savolainen
J
J
INSERM U454, Hôpital Arnaud de Villeneuve, Montpellier, France.
Kosonen
J
J
Kortekangas-Savolainen
O
O
Yssel
H
H
Bousquet
J
J
D000328:Adult; D000911:Antibodies, Monoclonal / Q000187:drug effects / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005387:Finland; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008351:Mannans / Q000276:immunology*; D008766:Methylmannosides / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D013223:Statistics as Topic; D013577:Syndrome
D000911:Antibodies, Monoclonal; D006683:HLA-DQ Antigens; D008351:Mannans; D008766:Methylmannosides; D007073:Immunoglobulin E; C008466:methylmannoside