Abstract
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 language | English |
|---|---|
| Pages (from-to) | 10033-10037 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 87 |
| Issue number | 24 |
| State | Published - Dec 1 1990 |
| Externally published | Yes |
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Keywords
- Interleukin 2 therapy
- Lymphokine gene regulation
ASJC Scopus subject areas
- Genetics
- General
Cite this
Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes. / Chatila, Talal; Castigli, Emanuela; Pahwa, Rajendra; Pahwa, Savita G; Chirmule, Narendra; Oyaizli, Naoki; Good, Robert A.; Geha, Raif S.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 24, 01.12.1990, p. 10033-10037.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes
AU - Chatila, Talal
AU - Castigli, Emanuela
AU - Pahwa, Rajendra
AU - Pahwa, Savita G
AU - Chirmule, Narendra
AU - Oyaizli, Naoki
AU - Good, Robert A.
AU - Geha, Raif S.
PY - 1990/12/1
Y1 - 1990/12/1
N2 - 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.
AB - 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.
KW - Interleukin 2 therapy
KW - Lymphokine gene regulation
UR - http://www.scopus.com/inward/record.url?scp=0025599933&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025599933&partnerID=8YFLogxK
M3 - Article
C2 - 2263604
AN - SCOPUS:0025599933
VL - 87
SP - 10033
EP - 10037
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 24
ER -