Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade

Figure 3

Deletion of donor-reactive T cells differs among donor strains. (a) Deletion of donor-reactive T cells was investigated through determination of the percentage of Vβ11⁺ and Vβ8.1/2⁺ CD4⁺ PBL by 2-color flow cytometric analysis 4 weeks after BMT. Deletion of Vβ11⁺ CD4⁺ PBL in Balb/c (, mHAg mismatched, ) and B10.D2 (, mHAg matched, ) BMC recipients developed to a similar dimension irrespective of differing mHAg disparities of donor to recipient. In mice which were transplanted with BMC of B10.A (, mHAg matched, ) a significant increase of early deletion compared to BMT of Balb/c (, mHAg mismatched) and B10.D2 (, mHAg matched) donors was observed ( versus Balb/c and B10.D2 BMC recipients). The percentage of Vβ8⁺ CD4⁺ cells was not significantly reduced in any group compared to naïve BL6 mice indicating the specificity of the deletion for superantigens presented by the donor. (b) Ten weeks after BMT the degree of deletion was significantly enhanced in long time chimeras after Balb/c and B10.D2 BMT but still was significantly less pronounced than in recipients of B10.A BMC. Mean percentages of Vβ11⁺ and Vβ8.1/2⁺ CD4⁺ PBL, interquartile range (box), and SD (whiskers) of long-term chimeras are shown as box-and-whisker blots. Representative data from one of two independent experiments. Statistical significance determined by log-rank test. versus Balb/c donors; versus week 4 after BMT (each group).

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