Journal
JOURNAL OF IMMUNOLOGY
Volume 166, Issue 2, Pages 1398-1404Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.166.2.1398
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Funding
- NHLBI NIH HHS [P01 HL 18646] Funding Source: Medline
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In murine allogeneic bone marrow transplantation recipients, treatment of the hosts with a nonmyeloablative regimen, including depleting anti-CD4 and anti-CD8 mAbs, allows establishment of long-term mixed chimerism and donor-specific tolerance. However, in the xenogeneic rat-to-mouse combination, additional anti-Thy1.2 and anti-NK1.1 mAbs are required. We have now attempted to identify the xenoresistant mouse cell populations that are targeted by anti-NK1.1 and anti-Thy1.2 mAbs. C57BL/6 (B6) wild-type, B6 TCR beta (-/-), and B6 TCR delta (-/-) mice received anti-CD4 and anti-CDS mAbs, followed by 3 Gy of whole body irradiation, 7 Gy of thymic irradiation, and transplantation of T cell-depleted rat bone marrow cells. Anti-NK1.1 and anti-Thy1.2 mAbs were additionally administered to some groups. Increased rat chimerism was observed in TCR delta (-/-) mice treated with anti-CD4, anti-CD8, and anti-NK1.1 mAbs compared with similarly treated TCR beta (-/-) mice. In TCR beta (-/-) mice, but not in TCR delta (-/-) mice, donor chimerism was increased by treatment with anti-Thy1.2 mAb, indicating that CD4(-)CD8(-)TCR gamma delta (+)Thy1.2(+)NK1.1(-) cells (gamma delta T cells) are involved in the rejection of rat marrow. In addition, chimerism was enhanced in both TCR beta (-/-) and TCR delta (-/-) mice treated with anti-CD4, anti-CD8, and anti-Thy1.2 mAbs by the addition of anti-NK1.1 mAb to the conditioning regimen. Donor-specific skin graft prolongation was enhanced by anti-Thy1.2 and anti-NK1.1 mAbs in TCR delta (-/-) mice. Therefore, in addition to CD4 and CD8 T cells, gamma delta T cells and NK cells play a role in resisting engraftment of rat marrow and the induction of xenograft tolerance in mice.
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