Coordinate regulation of the IL-4, IL-13, and IL-5 cytokine cluster in Th2 clones revealed by allelic expression patterns

被引:109
作者
Kelly, BL
Locksley, RM
机构
[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Immunol Microbiol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
关键词
D O I
10.4049/jimmunol.165.6.2982
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The cytokines IL-4, IL-13, and IL-5 are markers for the Th2 subset of effector T cells and are often expressed together. These cytokine genes are organized within 140 kb of orthologous DNA in both mouse and human. Using IL-1-expressing CD4(+) T cell clones derived from F-1 mice, we identified allelic polymorphisms for each of these cytokines and assessed the parental identity of the cytokine mRNAs, Both monoallelic and biallelic expression occurred for each gene and for an additional gene, IL-3, that lies with GM-CSF over 450 kh telomeric on the same chromosome. When coexpressed in T cell clones, IL-4 was expressed from the same allele as IL-13 or IL-5 in 81% of instances. In contrast, there was only 52% concordance of these three cytokines at the allelic level among clones that expressed IL-3, Independent expression of the cytokine alleles occurs commonly in T cells, but the clustered locus encompassing IL-4, IL-13, and IL-5 is subject to coordinate regulation.
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页码:2982 / 2986
页数:5
相关论文
共 30 条
[1]   Functional diversity of helper T lymphocytes [J].
Abbas, AK ;
Murphy, KM ;
Sher, A .
NATURE, 1996, 383 (6603) :787-793
[2]   Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation [J].
Agarwal, S ;
Rao, A .
IMMUNITY, 1998, 9 (06) :765-775
[3]   FLOW CYTOMETRIC DETERMINATION OF CYTOKINES IN ACTIVATED MURINE T-HELPER LYMPHOCYTES - EXPRESSION OF INTERLEUKIN-10 IN INTERFERON-GAMMA AND IN INTERLEUKIN-4-EXPRESSING CELLS [J].
ASSENMACHER, M ;
SCHMITZ, J ;
RADBRUCH, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (05) :1097-1101
[4]   Helper T cell differentiation is controlled by the cell cycle [J].
Bird, JJ ;
Brown, DR ;
Mullen, AC ;
Moskowitz, NH ;
Mahowald, MA ;
Sider, JR ;
Gajewski, TF ;
Wang, CR ;
Reiner, SL .
IMMUNITY, 1998, 9 (02) :229-237
[5]   Independent and epigenetic regulation of the interleukin-4 alleles in CD4+ T cells [J].
Bix, M ;
Locksley, RM .
SCIENCE, 1998, 281 (5381) :1352-1354
[6]   HETEROGENEITY OF SINGLE-CELL CYTOKINE GENE-EXPRESSION IN CLONAL T-CELL POPULATIONS [J].
BUCY, RP ;
PANOSKALTSISMORTARI, A ;
HUANG, GQ ;
LI, JM ;
KARR, L ;
ROSS, M ;
RUSSELL, JH ;
MURPHY, KM ;
WEAVER, CT .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (04) :1251-1262
[7]   SINGLE-CELL ANALYSIS OF CYTOKINE GENE COEXPRESSION DURING CD4(+) T-CELL PHENOTYPE DEVELOPMENT [J].
BUCY, RP ;
KARR, L ;
HUANG, GQ ;
LI, JM ;
CARTER, D ;
HONJO, K ;
LEMONS, JA ;
MURPHY, KM ;
WEAVER, CT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7565-7569
[8]   IDENTIFICATION OF A COMMON NUCLEOTIDE-SEQUENCE IN THE 3'-UNTRANSLATED REGION OF MESSENGER-RNA MOLECULES SPECIFYING INFLAMMATORY MEDIATORS [J].
CAPUT, D ;
BEUTLER, B ;
HARTOG, K ;
THAYER, R ;
BROWNSHIMER, S ;
CERAMI, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (06) :1670-1674
[9]   The human granulocyte-macrophage colony-stimulating factor gene is autonomously regulated in vivo by an inducible tissue-specific enhancer [J].
Cockerill, PN ;
Bert, AG ;
Roberts, D ;
Vadas, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15097-15102
[10]   A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site [J].
Duncliffe, KN ;
Bert, AG ;
Vadas, MA ;
Cockerill, PN .
IMMUNITY, 1997, 6 (02) :175-185