Severe combined immunodeficiency with selective T-cell cytokine genes.
A 4-y-old female with severe combined immunodeficiency disease had normal numbers of T cells in her circulation and normal T-cell subsets. However, her T cells proliferated poorly to mitogens and did not proliferate to antigens or to anti-CD3 MAb. IL-2 receptor expression was normal, but IL-2 synthesis was undetectable. The addition of recombinant IL-2 to a mitogen-stimulated culture resulted in normalization of the proliferative response. Northern blot analysis of total RNA derived from the patient's T cells revealed a weak or absent expression of mRNA coding for IL-2, IL-3, IL-4, and IL-5. In contrast, there were normal amounts of mRNA coding for granulocyte-macrophage colony-stimulating factor. Tumor necrosis factor and IL-6 production were also normal. Nuclear run-on transcriptional assays revealed markedly decreased levels of newly initiated nuclear transcripts coding for IL-2, IL-3, IL-4, and IL-5 and normal levels of granulocyte-macrophage colony-stimulating factor transcripts in the patient relative to control lymphocytes. Gel retardation assays suggest that the NFAT-1 nuclear transcription complex is abnormal in this patient. These results indicate that the patient suffers from a defect that affects the transcription of multiple T-cell lymphokines and suggest that abnormalities affecting the production of T-cell lymphokines may underlie some of the primary immunodeficiency diseases.
Castigli
E
E
Division of Immunology, Children's Hospital, Boston, Massachusetts 02115.
Geha
R S
RS
Chatila
T
T
D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger