Figure 6.

Engraftment of athymic nude mice with fetal thymus tissue from Bcl-3, NF-κB2 double knockout (dKO) causes multi-organ inflammation. (a) Nude mice engrafted with (T-depleted) fetal thymus lobes from NF-κB2 KO and dKO mice (with and without OT-I transgene) were monitored and the surviving proportion was plotted. (b) H&E-stained sections from liver and lung of nude mice engrafted 6 weeks prior with fetal thymus from NF-κB2 KO or dKO mice. (c) Splenic T cells from nude mice engrafted 5 weeks prior with fetal thymus from NF-κB2 KO or dKO mice were gated on CD4⁺ and CD8⁺and analyzed for expression of CD44 and CD62L by flow cytometry. Representative examples are shown (b, c). (d) Nude mice engrafted with fetal thymus from dKO mice exhibited elevated autoantibodies when compared to nudes engrafted with NF-κB2 KO fetal thymus. Serum was collected from matched nudes between 5 ½ and 7 weeks post transplantation. Serum antibody titers to the indicated autoantigens were determined with ELISA assays (1:100 dilution for anti-IgG, 1:200 dilution for anti-insulin; p=0.047 and p=0.03, respectively). (e) H&E-stained sections from liver and lung of nude mouse engrafted 10 weeks prior with one fetal thymic lobe from a dKO mouse or with the other fetal thymic lobe from the same dKO mouse and one lobe from a WT mouse. (f) Splenic T cells were isolated from the thymic stroma-engrafted nude mouse shown in (e) were gated on CD4⁺ and CD8⁺and analyzed for expression of CD44 and CD62L by flow cytometry. The engrafted nude mouse shown in (e,f) is a representative example of 6 other such matched transfers.