Novel immune deficiencies: defective transcription of lymphokine genes.
A 4-year-old female with severe combined immunodeficiency (SCID) had normal numbers of T cells in 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. Interleukin-2 (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 (GM-CSF). Tumor necrosis factor and IL-6 production was 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 GM-CSF transcripts in patient relative to control lymphocytes. These results indicate that the patient's T cells suffered from a defect affecting 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.
Geha
R S
RS
Division of Immunology, Children's Hospital, Boston, Massachusetts.
Castigli
E
E
Chatila
T
T
D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007377:Interleukin-3 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008222:Lymphokines / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic; D015854:Up-Regulation
D007376:Interleukin-2; D007377:Interleukin-3; D008222:Lymphokines; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor