Bone marrow engraftment and GVHD across a concordant xenogeneic barrier (mouse to rat)

LI,

doi:10.1016/0963-6897(96)82285-8

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“…Interestingly, positive selection of developing lymphocytes occurs efficiently, with both rat and mouse T cells selected for immune restriction to host (mouse) MHC Ags (22,23). The restriction of Ag presentation to host elements present in mixed xenogeneic chimeras, prepared as outlined in this manuscript, has been demonstrated to result in a relative resistance to graft-vs-host disease and to the superior immunocompetence present following mixed reconstitution (19,22,23,41). These mixed xenogeneic chimeras demonstrate that both mouse and rat T cells that develop in a mixed xenogeneic environment can recognize virally infected cells of the host by the generation of viral-specific CTL activity in vivo (22).…”

Section: Figurementioning

confidence: 99%

Mixed Xenogeneic Chimerism Induces Donor-Specific Humoral and Cellular Immune Tolerance for Cardiac Xenografts

Colson

Huang

et al. 2004

The Journal of Immunology

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Xenotransplantation has been suggested as a potential solution to the critical shortage of donor organs. However, success has been limited by the vigorous rejection response elicited against solid organs transplanted across species barriers. Mixed xenogeneic bone marrow chimeras resulting from the transplantation of a mixture of host and donor marrow (B10 mouse + F344 rat → B10 mouse) results in donor-specific cross-species transplantation tolerance for subsequent nonvascularized skin and islet grafts. Furthermore, compared with fully xenogeneic chimeras (rat → mouse), mixed xenogeneic chimeras exhibit superior immunocompetence for infectious agents in vivo and in vitro, suggesting that the immune system is intact. The ability to establish long-term humoral and cellular tolerance for primarily vascularized xenografts in vivo, in the setting of both recipient and donor Ig and effector cell production, has not previously been characterized. Mixed xenogeneic chimeras exhibit donor-specific humoral tolerance as evident by the absence of anti-donor Ab and Ab-dependent donor-specific cytotoxicity in vitro and intravascular IgM deposition within donor-strain (F344) cardiac xenografts in vivo. F344 cardiac xenografts are accepted (median ≥180 days) without clinical or histologic evidence of rejection, suggesting cellular tolerance. In contrast, MHC-disparate third-party mouse (B10.BR) and rat (ACI or WF) grafts are rejected (median of 23 and 41 days, respectively) in association with extensive mononuclear cell infiltration and vascular deposits of mouse IgM. These results demonstrate that mixed xenogeneic chimerism establishes donor-specific humoral and cellular tolerance and permits the successful transplantation of even primarily vascularized xenografts in the setting of intact Ab production.

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Section: Figurementioning

confidence: 99%