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PMID: 8901605 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 22 ·1996-10-29 ·Pages 12467-72

Gorham JD, Güler ML, Steen RG, Mackey AJ, Daly MJ, Frederick K, Dietrich WF, Murphy KM

Abstract

Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B10.D2) favoring Th1 development and others (e.g., BALB/c) favoring Th2 development. Recently we found that B10.D2 exhibit an intrinsically greater capacity to maintain interleukin 12 (IL-12) responsiveness under neutral conditions in vitro compared with BALB/c T cells, allowing for prolonged capacity to undergo IL-12-induced Th1 development. To begin identification of the loci controlling this genetic effect, we used a T-cell antigen receptor-transgenic system for in vitro analysis of intercrosses between BALB/c and B10.D2 mice and have identified a locus on murine chromosome 11 that controls the maintenance of IL-12 responsiveness, and therefore the subsequent Th1/Th2 response. This chromosomal region is syntenic with a locus on human chromosome 5q31.1 shown to be associated with elevated serum IgE levels, suggesting that genetic control of Th1/Th2 differentiation in mouse, and of atopy development in humans, may be expressed through similar mechanisms.

MeSH Terms
Animals Chromosome Mapping Chromosomes/chemistry Chromosomes, Human, Pair 5 Female Humans Interleukin-12/pharmacology Male Mice Mice, Inbred BALB C Phenotype Polymorphism, Restriction Fragment Length Th1 Cells/cytology Th2 Cells/cytology
Chemicals
Interleukin-12
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gorham J D
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Güler M L
Steen R G
Mackey A J
Daly M J
Frederick K
Dietrich W F
Murphy K M
References (44)
44 references, click to expand
  1. Effect of combinations of inbred strain, antigen, and antigen dose on immune responsiveness and reagin production in the mouse. A potential mouse model for immune aspects of human atopic allergy.
    Int Arch Allergy Appl Immunol. 1970;39(2-3):156-71 PMID: 4097264
  2. Genetic analysis of autoimmune type 1 diabetes mellitus in mice.
    Nature. 1991 Jun 13;351(6327):542-7 PMID: 1675432
  3. Immunological regulation and control of experimental leishmaniasis.
    Int Rev Exp Pathol. 1986;28:79-116 PMID: 3516912
  4. MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations.
    Genomics. 1987 Oct;1(2):174-81 PMID: 3692487
  5. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements.
    Cell. 1988 Sep 9;54(6):903-13 PMID: 3409321
  6. Cloned L3T4+ T lymphocytes protect mice against Listeria monocytogenes by secreting IFN-gamma.
    J Immunol. 1988 Nov 1;141(9):3203-7 PMID: 2459247
  7. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.
    J Exp Med. 1989 Jan 1;169(1):59-72 PMID: 2521244
  8. Clustering of cytokine genes on mouse chromosome 11.
    J Exp Med. 1990 Apr 1;171(4):1301-14 PMID: 1969921
  9. Mendelian factors underlying quantitative traits in tomato: comparison across species, generations, and environments.
    Genetics. 1991 Jan;127(1):181-97 PMID: 1673106
  10. A genetic map of the mouse suitable for typing intraspecific crosses.
    Genetics. 1992 Jun;131(2):423-47 PMID: 1353738
  11. Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection.
    Immunol Rev. 1992 Jun;127:183-204 PMID: 1354651
  12. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.
    J Exp Med. 1992 Oct 1;176(4):1091-8 PMID: 1328464
  13. Localization of the human chromosome 5q genes Gabra-1, Gabrg-2, Il-4, Il-5, and Irf-1 on mouse chromosome 11.
    Mamm Genome. 1992;3(10):604-7 PMID: 1358285
  14. itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11194-8 PMID: 1280821
  15. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages.
    Science. 1993 Apr 23;260(5107):547-9 PMID: 8097338
  16. Recombinant interleukin 12 cures mice infected with Leishmania major.
    J Exp Med. 1993 May 1;177(5):1505-9 PMID: 8097524
  17. Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response.
    J Exp Med. 1993 Jun 1;177(6):1797-802 PMID: 8098733
  18. Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming.
    Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10188-92 PMID: 7901851
  19. Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection.
    J Exp Med. 1994 Feb 1;179(2):447-56 PMID: 7905017
  20. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations.
    Science. 1994 May 20;264(5162):1152-6 PMID: 8178175
  21. Acquisition of lymphokine-producing phenotype by CD4+ T cells.
    Annu Rev Immunol. 1994;12:635-73 PMID: 7912089
  22. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis.
    Science. 1994 Aug 26;265(5176):1237-40 PMID: 7520605
  23. Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7011-5 PMID: 1908085
  24. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.
    N Engl J Med. 1992 Jan 30;326(5):298-304 PMID: 1530827
  25. Inflammatory leukocytes and cytokines in the peptide-induced disease of experimental allergic encephalomyelitis in SJL and B10.PL mice.
    Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):574-8 PMID: 1370583
  26. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an alpha beta T-cell-receptor transgenic system.
    Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6065-9 PMID: 1385868
  27. A genetic map of the mouse with 4,006 simple sequence length polymorphisms.
    Nat Genet. 1994 Jun;7(2 Spec No):220-45 PMID: 7920646
  28. Evidence for a locus regulating total serum IgE levels mapping to chromosome 5.
    Genomics. 1994 Sep 15;23(2):464-70 PMID: 7835897
  29. T cell genetic background determines default T helper phenotype development in vitro.
    J Exp Med. 1995 Feb 1;181(2):713-21 PMID: 7836924
  30. Genetic analysis of atopy and asthma as quantitative traits and ordered polychotomies.
    Ann Hum Genet. 1994 Oct;58(Pt 4):359-68 PMID: 7864591
  31. An HMG-box-containing T-cell factor required for thymocyte differentiation.
    Nature. 1995 Mar 2;374(6517):70-4 PMID: 7870176
  32. A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity.
    Immunity. 1994 Apr;1(1):73-83 PMID: 7889402
  33. Regulation of the development of type 2 T-helper cells in allergy.
    Curr Opin Immunol. 1994 Dec;6(6):838-46 PMID: 7710707
  34. High-resolution genetic mapping of complex traits.
    Am J Hum Genet. 1995 May;56(5):1212-23 PMID: 7726179
  35. T helper cell subsets in insulin-dependent diabetes.
    Science. 1995 May 26;268(5214):1185-8 PMID: 7761837
  36. Developmental commitment to the Th2 lineage by extinction of IL-12 signaling.
    Immunity. 1995 Jun;2(6):665-75 PMID: 7796298
  37. Approaches to mapping genes for allergy and asthma.
    Am J Respir Crit Care Med. 1995 Jul;152(1):411-3 PMID: 7599858
  38. Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy.
    N Engl J Med. 1995 Oct 5;333(14):894-900 PMID: 7666875
  39. Genetic analysis of experimental allergic encephalomyelitis in mice.
    J Immunol. 1995 Oct 15;155(8):4046-51 PMID: 7561115
  40. Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity.
    J Exp Med. 1996 Jan 1;183(1):109-17 PMID: 8551213
  41. Genetic susceptibility to Leishmania: IL-12 responsiveness in TH1 cell development.
    Science. 1996 Feb 16;271(5251):984-7 PMID: 8584935
  42. Genetic control of Leishmania major infection in congenic, recombinant inbred and F2 populations of mice.
    Eur J Immunogenet. 1993 Oct;20(5):335-48 PMID: 9098402
  43. Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production.
    Proc Natl Acad Sci U S A. 1991 May 15;88(10):4538-42 PMID: 1827920
  44. Regulation of IgE antibody production by serum molecules. II. Strain-specificity of the suppressive activity of serum from complete freund's adjuvant-immune low responder mouse donors.
    J Immunol. 1978 Jun;120(6):2060-7 PMID: 659892
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.93.22.12467
Published
1996-10-29
Pages
12467-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38015
Subset
IM
Grants
NIAID NIH HHS · AI31238 · United States
NIAID NIH HHS · AI34580 · United States
NIDDK NIH HHS · DK20579 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.22.12467 PMC Full Text View journal details
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