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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 languageEnglish
Pages (from-to)10033-10037
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number24
StatePublished - Dec 1 1990
Externally publishedYes

Fingerprint

Lymphokines
T-Lymphocytes
Interleukin-2
Genes
Messenger RNA
CD3 Antigens
Trans-Activators
Interleukin-3
Interleukin-5
Opportunistic Infections
Granulocyte-Macrophage Colony-Stimulating Factor
Mitogens
Interleukin-4
Northern Blotting
Interferons
RNA
Phenotype
Membranes

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 journalArticle

Chatila, Talal ; Castigli, Emanuela ; Pahwa, Rajendra ; Pahwa, Savita G ; Chirmule, Narendra ; Oyaizli, Naoki ; Good, Robert A. ; Geha, Raif S. / Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes. In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 24. pp. 10033-10037.
@article{8a0d31749afa42bdb419b222a5ba335c,
title = "Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes",
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.",
keywords = "Interleukin 2 therapy, Lymphokine gene regulation",
author = "Talal Chatila and Emanuela Castigli and Rajendra Pahwa and Pahwa, {Savita G} and Narendra Chirmule and Naoki Oyaizli and Good, {Robert A.} and Geha, {Raif S.}",
year = "1990",
month = "12",
day = "1",
language = "English",
volume = "87",
pages = "10033--10037",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "24",

}

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 -