Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hackstein, H. et al.

Normal donor bone marrow is superior to Flt3 ligand-mobilized bone marrow in prolonging heart allograft survival when combined with anti-CD40L (CD154).

Flt3 ligand (FL) administration markedly increases bone marrow (BM) stem cells and immature dendritic cells. We investigated the influence of CD40-CD40Ligand (CD154) pathway blockade on antidonor immunity, cytokine production, microchimerism and heart graft survival in BALB/c (H2d) recipients of fully allogeneic C57BL/10 (H2b) FL-mobilized BM (FL-BM) or normal BM. Anti-CD40L mAb strongly suppressed anti-donor T-cell proliferative responses in recipients of either normal or FL-BM, but was less efficient in inhibiting antidonor cytolytic T-cell (CTL) activity, especially in recipients of FL-BM. Interestingly, CD40L blockade was more effective in recipients of multiple compared with single donor BM infusions. Anti-donor cytokine responses revealed complete impairment of IFN-gamma, IL-4 and IL-10 production in recipients of normal BM and CD40L mAb. By contrast, and in agreement with the CTL data, mice given FL-BM retained ability to produce IFN-gamma CD40-CD40L blockade did not promote microchimerism, as evidenced by immunohistology and real time polymerase chain reaction. Nevertheless, anti-CD40L mAb enhanced heart allograft survival in recipients of FL-BM, but the effect was inferior to that achieved with normal BM. These data provide insight into the influence of growth factor-expanded donor BM and costimulation blockade on antidonor immune reactivity and transplant outcome. The comparatively poor outcome obtained using FL-BM plus anti-CD40L mAb in this model may be ascribed to the failure of effectively interdicting antidonor CTL activity.[1]

References

Normal donor bone marrow is superior to Flt3 ligand-mobilized bone marrow in prolonging heart allograft survival when combined with anti-CD40L (CD154). Hackstein, H., Wang, Z., Morelli, A.E., Kaneko, K., Takayama, T., Colvin, B.L., Bein, G., Thomson, A.W. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2002) [Pubmed]

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