Home LiteratureArticle Details
PMID: 10840051 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Multiple differences in gene expression in regulatory Valpha 24Jalpha Q T cells from identical twins discordant for type I diabetes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 13 ·2000-06-20 ·Pages 7411-6

Wilson SB, Kent SC, Horton HF, Hill AA, Bollyky PL, Hafler DA, Strominger JL, Byrne MC

Abstract

Quantitative and qualitative defects in CD1d-restricted T cells have been demonstrated in human and murine autoimmune diseases. To investigate the transcriptional consequences of T cell receptor activation in human Valpha24JalphaQ T cell clones, DNA microarrays were used to quantitate changes in mRNA levels after anti-CD3 stimulation of clones derived from identical twins discordant for type 1 diabetes and IL-4 secretion. Activation resulted in significant modulation of 226 transcripts in the IL-4 secreting clone and 86 in the IL-4-null clone. Only 28 of these genes were in common. The differences observed suggest both ineffective differentiation of diabetic Valpha24JalphaQ T cells and a role for invariant T cells in the recruitment and activation of cells from the myeloid lineage.

MeSH Terms
Diabetes Mellitus, Type 1/genetics,immunology Gene Expression Regulation/immunology Humans Immunoglobulin Variable Region/genetics,immunology Receptors, Antigen, T-Cell, alpha-beta/genetics,immunology T-Lymphocytes/immunology Twins
Chemicals
Immunoglobulin Variable Region Receptors, Antigen, T-Cell, alpha-beta
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wilson S B
Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA. [email protected]
Kent S C
Horton H F
Hill A A
Bollyky P L
Hafler D A
Strominger J L
Byrne M C
References (30)
30 references, click to expand
  1. Mouse CD1-specific NK1 T cells: development, specificity, and function.
    Annu Rev Immunol. 1997;15:535-62 PMID: 9143699
  2. CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4.
    Immunity. 1997 Apr;6(4):469-77 PMID: 9133426
  3. Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells.
    J Exp Med. 1997 Jul 7;186(1):109-20 PMID: 9207002
  4. Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11227-32 PMID: 9326591
  5. Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors.
    Science. 1997 Nov 28;278(5343):1623-6 PMID: 9374462
  6. T-cell subsets: transcriptional control in the Th1/Th2 decision.
    Curr Biol. 1997 Nov 1;7(11):R729-32 PMID: 9382795
  7. Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes.
    Nature. 1998 Jan 8;391(6663):177-81 PMID: 9428763
  8. Inhibition of T cell activation by pharmacologic disruption of the MEK1/ERK MAP kinase or calcineurin signaling pathways results in differential modulation of cytokine production.
    J Immunol. 1998 Mar 15;160(6):2579-89 PMID: 9510155
  9. alpha/beta-T cell receptor (TCR)+CD4-CD8- (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10.
    J Exp Med. 1998 Apr 6;187(7):1047-56 PMID: 9529321
  10. T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells.
    J Exp Med. 1998 May 18;187(10):1721-7 PMID: 9584150
  11. Jaks and STATs: biological implications.
    Annu Rev Immunol. 1998;16:293-322 PMID: 9597132
  12. Expression monitoring by hybridization to high-density oligonucleotide arrays.
    Nat Biotechnol. 1996 Dec;14(13):1675-80 PMID: 9634850
  13. A genome-wide transcriptional analysis of the mitotic cell cycle.
    Mol Cell. 1998 Jul;2(1):65-73 PMID: 9702192
  14. CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24 J alpha Q T cell receptor alpha chains.
    J Exp Med. 1998 Sep 7;188(5):867-76 PMID: 9730888
  15. The transcription factor NFAT4 is involved in the generation and survival of T cells.
    Immunity. 1998 Sep;9(3):295-304 PMID: 9768749
  16. Overexpression of natural killer T cells protects Valpha14- Jalpha281 transgenic nonobese diabetic mice against diabetes.
    J Exp Med. 1998 Nov 16;188(10):1831-9 PMID: 9815260
  17. Dissecting the regulatory circuitry of a eukaryotic genome.
    Cell. 1998 Nov 25;95(5):717-28 PMID: 9845373
  18. Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development.
    Immunity. 1998 Nov;9(5):627-35 PMID: 9846484
  19. The transcriptional program in the response of human fibroblasts to serum.
    Science. 1999 Jan 1;283(5398):83-7 PMID: 9872747
  20. Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation.
    EMBO J. 1999 Jan 15;18(2):420-32 PMID: 9889198
  21. Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2907-12 PMID: 10077610
  22. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4240-5 PMID: 10200246
  23. Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.
    Science. 1999 Apr 23;284(5414):638-41 PMID: 10213685
  24. A defect in interleukin 12-induced activation and interferon gamma secretion of peripheral natural killer T cells in nonobese diabetic mice suggests new pathogenic mechanisms for insulin-dependent diabetes mellitus.
    J Exp Med. 1999 Oct 4;190(7):963-72 PMID: 10510086
  25. The development of autoimmunity in C57BL/6 lpr mice correlates with the disappearance of natural killer type 1-positive cells: evidence for their suppressive action on bone marrow stem cell proliferation, B cell immunoglobulin secretion, and autoimmune symptoms.
    J Exp Med. 1993 Jan 1;177(1):155-64 PMID: 8418197
  26. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.
    Cell. 1997 May 16;89(4):587-96 PMID: 9160750
  27. Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.
    J Immunol. 1996 May 15;156(10):4035-40 PMID: 8621946
  28. Interferon gamma production by natural killer (NK) cells and NK1.1+ T cells upon NKR-P1 cross-linking.
    J Exp Med. 1996 May 1;183(5):2391-6 PMID: 8642351
  29. Immunoglobulin E production in the absence of interleukin-4-secreting CD1-dependent cells.
    Science. 1997 Feb 14;275(5302):977-9 PMID: 9020080
  30. Association between alphabetaTCR+CD4-CD8- T-cell deficiency and IDDM in NOD/Lt mice.
    Diabetes. 1997 Apr;46(4):572-82 PMID: 9075796
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.120161297
Email
[email protected]
Published
2000-06-20
Pages
7411-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16559
Subset
IM
Grants
NIAID NIH HHS · R01 AI045051 · United States
NIAID NIH HHS · R01 AI44447 · United States
NIDDK NIH HHS · R01 DK52127 · United States
NCI NIH HHS · R35 CA47554 · United States
Corrections
CommentIn
PMID: 10860950
External Links
PubMed source DOI: 10.1073/pnas.120161297 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2