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A partial conditioning approach to achieve mixed chimerism in the rat: depletion of host natural killer cells significantly reduces the amount of total body irradiation required for engraftment.

Abstract：

BACKGROUND:Mixed allogeneic bone marrow chimerism induces tolerance to solid organ grafts. Although we previously reported that partially ablative conditioning with 700 cGy of total body irradiation (TBI) is sufficient to allow for bone marrow engraftment in mice, we determined that a minimum of 1000 cGy was required in the rat. Because T cells and NK cells are critical in bone marrow graft rejection, our purpose was to examine whether targeting of radioresistant NK cells and/or T cells in the recipient hematopoietic microenvironment would reduce the TBI dose required for engraftment of allogeneic rat bone marrow. METHODS:Wistar Furth rats received either anti-NK3.2.3 monoclonal antibodies on days -3 and -2, anti-lymphocyte serum on day -5, a combination of both or no pretreatment. TBI was performed on day 0 and rats were reconstituted with 100x10(6) T cell-depleted bone marrow cells from ACI donors. RESULTS:Engraftment of T cell-depleted rat bone marrow was readily achieved in animals conditioned with 1000 cGy TBI alone (12/12) and the level of donor chimerism averaged 89%. At 900 cGy TBI alone only one of eight recipients engrafted. In striking contrast, 11 of 12 animals pretreated with anti-NK monoclonal antibodies and irradiated with 900 cGy showed donor chimerism at a mean level of 41%. No further enhancement of bone marrow engraftment could be achieved when recipients were pretreated with antilymphocyte serum alone or antilymphocyte serum plus anti-NK monoclonal antibodies. Mixed allogeneic chimeras exhibited stable multilineage chimerism and donor-specific tolerance to subsequent cardiac allografts. CONCLUSION:Specific targeting of radioresistant host NK cells allows for a significant reduction of the TBI dose required for allogeneic bone marrow engraftment.

journal_name

Transplantation

journal_title

Transplantation

authors

Neipp M,Gammie JS,Exner BG,Li S,Chambers WH,Pham SM,Ildstad ST

doi

10.1097/00007890-199908150-00008

subject

Has Abstract

pub_date

1999-08-15 00:00:00

pages

369-78

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

杂志文章

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A partial conditioning approach to achieve mixed chimerism in the rat: depletion of host natural killer cells significantly reduces the amount of total body irradiation required for engraftment.