Dendritic cell differentiation and immune tolerance to insulin-related peptides in Igf2-deficient mice.
There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in the control of T cell differentiation. To further study the immunoregulatory function of this growth factor, we analyzed the immune system of Igf2-/- mice. Phenotypically, some immunological parameters such as lymphoid organ morphology and cellularity were unaltered in Igf2-/- mice, but an increase of CD8+ cells and a decrease of B220+ cells were observed in spleen. In vitro, the development of bone marrow-derived dendritic cells was affected by the absence of Igf2 expression. After maturation, a higher percentage of immature dendritic cells was observed in Igf2-/- population, together with a secondary decrease in allogenic T cell proliferation. Activation of T cells was also affected by the lack of expression of this growth factor. The profile of B cell response in mutant mice immunized with IGF-2 evidenced a T-dependent profile of anti-IGF-2 Abs that was absent in Igf2+/+ mice. The influence of IGF-2 upon tolerance to insulin was also assessed in this model, and this showed that IGF-2 also intervenes in tolerance to insulin. The presence of a T-dependent response in Igf2-deficient mice should allow cloning of specific "forbidden" T CD4+ lymphocytes directed against IGF-2, as well as further investigation of their possible pathogenic properties against insulin family.
Hansenne
Isabelle
I
Center of Immunology, University of Liege, Liege-Sart Tilman, Belgium. Isabelle.Hansenne@ulg.ac.be
Renard-Charlet
Chantal
C
Greimers
Roland
R
Geenen
Vincent
V
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D066298:In Vitro Techniques; D007328:Insulin / Q000276:immunology*; D007335:Insulin-Like Growth Factor II / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D018076:DNA, Complementary; D007328:Insulin; D007335:Insulin-Like Growth Factor II