Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.
Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.
Del Prete
G
G
Clinica Medica III, University of Florence, Policlinico Careggi, Italy.
Tiri
A
A
Maggi
E
E
De Carli
M
M
Macchia
D
D
Parronchi
P
P
Rossi
M E
ME
Pietrogrande
M C
MC
Ricci
M
M
Romagnani
S
S
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia / Q000097:blood*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D007958:Leukocyte Count; D010835:Phytohemagglutinins / Q000494:pharmacology; D013577:Syndrome; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D007371:Interferon-gamma