Abstract

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. The Journal of Immunology, 2006, 176: 4651–4657. I nsulin-like growth factors 1 and 2 (IGF-1/2)3 are members ofthe insulin hormone family that exert a prominent role in fetaland postnatal development (1, 2). Null mutant mice for Igf1 show a marked growth deficiency with 60 % of normal body weight, a variable neonatal lethality frequency depending on ge-