Immunologic changes in rats undergoing BMT. (A) Anti-MOG IgG titers in different immunization and transplantation settings. BMT leads to strong reduction of autoantibody titers, which persist also after secondary challenge (time point day 0: naive DA rats n = 4; time point day 15: EAE without BMT n = 6; time point day 123: DA BM n = 8, ACI BM n = 6, no BM n = 8; time point day 154: DABM n = 6,ACI BM n = 5, no BM n = 6). EAE leads to an increase in anti-MOG antibody titers (P < .002). On day 123 and day 154, groups undergoing BMT showed strongly reduced autoantibody titers compared with rats not receiving transplants (each P < .001). Rats that received transplants as naive animals (day 23 after immunization) and were subsequently induced with EAE did not show a reduction of autoantibodies compared with controls not receiving transplants (day 15 after immunization) (NS). (B) Reduction of anti-MOG 1-125 IgG, IgG1, IgG2a, and IgG2c levels in both groups receiving transplants at day 115 after immunization (day 98 after BMT: DA BM graft n = 6, ACI BM graft n = 5) compared with the group not receiving transplants (n = 6) (each P < .001, ANOVA). No significant differences for IgG2b between the DA/ACI BM treatment groups were observed. Only the group not undergoing BMT had higher levels of IgG2b and IgG2c antibodies (P < .001, ANOVA). (C) In lymphocytes derived from blood the percentage of B cells was increased while the percentage of CD4⁺ and CD8⁺ T cells was reduced when comparing rats receiving transplants and controls. Significant changes were seen for B cells (P < .001,ANOVA), CD4⁺ cells (P < .001,ANOVA), and CD8⁺ cells (P = .04,ANOVA) between rats receiving transplants and those not receiving transplants. (D) Lymphocytes isolated from draining lymph nodes of rats were analyzed by fluorescence-activated cell sorting (FACS) (DA BM graft n = 5, ACI BM graft n = 6, naive BMT n= 5, no BMT n = 6). The relative size of the CD4⁺ T-cell compartment was reduced in rats undergoing BMT if compared with controls, while the relative size of the B-cell compartment was enlarged compared with controls. The differences between the group not receiving transplants and the groups receiving transplants were significant in the T-cell (CD4 and CD8) and B-cell compartment (for all P < .001, ANOVA). (E) DA BM and ACI BM grafted rats at the height of EAE had an increase in numbers of MOG 73-90-specific IFN-γ-secreting cells related to numbers of MOG 1-125-specific IFN-γ-secreting cells compared with the other investigated groups (P < .001, ANOVA) (DA BM n = 15, ACI BM n = 10, no BMT n = 16, naive DA BMT n = 5). In contrast, the numbers of MOG 91-108-specific IFN-γ-secreting cells in relation to MOG 1-125-specific IFN-γ-secreting cells did not differ between the groups (NS, ANOVA). (F) Only DA rats immunized with MOG 91-108 (n = 5) developed EAE but not DA rats immunized with MOG 73-90 (n = 5) (cumulative score day 0 to 18 after immunization, P < .001, t test).