T helper type 2-like cells and therapeutic effects of interferon-gamma in combined immunodeficiency with hypereosinophilia (Omenn's syndrome).
We characterized the defects of CD4+ cells in a 17-month-old girl suffering from combined immunodeficiency with hypereosinophilia (Omenn's syndrome). Because the vast majority of peripheral blood CD4+ cells expressed the CD45R0 isoform, we purified circulating CD4+ CD45R0+ cells from the patient and healthy individuals in order to compare their production of cytokines. The patient's CD4+ CD45R0+ cells spontaneously produced high levels of interleukin-5 (IL-5) in vitro (1600 pg/ml after 24 h of culture) and this was associated with the presence of IL-5 in serum (323 pg/ml). After stimulation with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187, they produced higher levels of IL-4 (306 vs. 55 +/- 4 pg/ml) and IL-5 (2900 vs. 213 +/- 72 pg/ml) and lower levels of IL-2 (17 vs. 63 +/- 17 IU/ml) and interferon-gamma (IFN-gamma) (16 vs. 299 +/- 70 IU/ml) than controls CD4+ CD45R0+ cells. This T helper type 2 (Th2) pattern was confirmed by the detection using reverse polymerase chain reaction of IL-4, IL-5 and IL-10 mRNA within peripheral blood mononuclear cells. During a therapeutic trial with human IFN-gamma (40 micrograms/day) which ameliorated the clinical status of the patient, we observed a down-regulation of the in vivo expression of IL-5 and IL-10, a normalization of the eosinophil count and an improvement of the T cell response to phytohemagglutinin. This observation indicates for the first time that Th2-like cells might be involved in certain forms of congenital immunodeficiency and that IFN-gamma might down-regulate their activities in vivo.
Schandené
L
L
Hôpital Erasme-Department of Immunology, Brussels, Belgium.
Ferster
A
A
Mascart-Lemone
F
F
Crusiaux
A
A
Gérard
C
C
Marchant
A
A
Lybin
M
M
Velu
T
T
Sariban
E
E
Goldman
M
M
D015704:CD4 Antigens / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004802:Eosinophilia / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000628:therapy*; D007223:Infant; D007371:Interferon-gamma / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000032:analysis; D013577:Syndrome; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015704:CD4 Antigens; D016207:Cytokines; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens