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International Immunology, Vol. 12, No. 11, 1613-1622, November 2000
© 2000 Japanese Society for Immunology

NKT lymphocyte ontogeny and function are impaired in low antibody-producer Biozzi mice: gene mapping in the interval-specific congenic strains raised for immunomodulatory genes

Luiza M. Araujo, Anne Puel, Christine Gouarin1, Agathe Hameg1, Jean-Claude Mevel, Yasuhiko Koezuka2, Jean-Francois Bach1, Denise Mouton and André Herbelin1

INSERM U255, Institut Curie, 75248 Paris Cedex 05, France
1 INSERM U25 and Centre Claude Bernard, Hôpital Necker, 161 rue de Sèvres 75743 Paris Cedex 15, France
2 Pharmaceutical Research Laboratory, Kirin Brewery Co, Takasaki-shi, 370-1295 Gunma, Japan

Correspondence to: A. Herbelin

NKT cells are CD4+ or CD4–CD8– CD1d-restricted lymphocytes, characterized by the property to rapidly produce IL-4 and IFN-{gamma} in response to TCR ligation. This IL-4 burst is lacking in autoimmunity-prone SJL and NOD strains of mice, which suggests an immunoregulatory role for NKT cells. The NKT cell status was thus investigated in the genetically selected high (H) and low (L) antibody-producer mice. The results show that (i) the frequency of cells expressing the NKT cell markers is 3- to 4-fold lower in thymus and spleen from L than H mice, (ii) L mice spleen cells did not produce IL-4 following injection of anti-TCR{alpha}ß antibody, and (iii) L mice thymus and spleen cells failed to produce IL-4 after in vitro stimulation by anti-TCR{alpha}ß antibody or {alpha}-galactosylceramide, a newly described NKT cell ligand. These parameters were investigated in six interval-specific congenic strains raised for the quantitative trait loci which contain the immunomodulatory genes responsible for the high/low antibody production phenotypes. IL-4 production recovery occurred only in the congenic strain in which the H origin chromosome 4 segment was introgressed on the L background. This finding was not due to increased NKT cell frequency but appeared dependent of antigen-presenting cells in co-culture experiments. This result strongly suggests the presence of gene(s) modulating NKT function on chromosome 4, close to several genes predisposing to autoimmunity.

Keywords: antigen-presenting cell, Biozzi mice, gene mapping, IL-4, NKT cell

Transmitting editor: M. Taniguchi


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