Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes

Talal Chatila, Emanuela Castigli, Rajendra Pahwa, Savita Pahwa, Narendra Chirmule, Naoki Oyaizli, Robert A. Good, Raif S. Geha

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The circulating T lymphocytes of a female child with recurrent opportunistic infections were normal in number and phenotype but exhibited poor proliferation and Decreased synthesis of the T-cell growth factor interleukin (IL) 2 in response to mitogens. Recombinant IL-2 fully restored the proliferative responses of her T cells, suggesting that her poor Immune function was related to IL-2 deficiency. Northern blot analysis of total cellular RNA from the patient's T cells revealed markedly decreased levels of IL-2 mRNA of normal size. In addition, mRNA levels of other lymphokines selectively expressed by T cells, which include IL-3, IL-4, and IL-5, were either severely depressed or absent. The levels of interferon γ mRNA were moderately decreased, while those of granulocyte-macrophage colony stimulating factor, a lymphokine the production of which is not restricted to T cells, were unaffected. The decreased level of lymphokine mRNA in the patient's T lymphocytes was not from enhanced catabolism but resulted from a diminution in the transcription rate of the affected lymphokine genes. Normal transduction via the T-cell recep-tor/CD3 complex of biochemical signals necessary for the initiation of lymphokine gene transcription indicated that the defect was distal to the membrane signal-transducing apparatus. The defect is hypothesized to involve a T-cell-specific trans-acting regulatory factor required for transcription of the affected lymphokine genes.

Original languageEnglish (US)
Pages (from-to)10033-10037
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - 1990
Externally publishedYes


  • Interleukin 2 therapy
  • Lymphokine gene regulation

ASJC Scopus subject areas

  • Genetics
  • General


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