期刊
JOURNAL OF IMMUNOLOGY
卷 172, 期 12, 页码 7451-7458出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.172.12.7451
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资金
- NHLBI NIH HHS [F32 HL074694, F32 HL 074694, R01 HL 67976, R01 HL067976] Funding Source: Medline
- NIDDK NIH HHS [P30 DK057516, R01 DK033470, R01 DK 33470, P30 DK 57516] Funding Source: Medline
CD4 T cells are both necessary and sufficient to mediate acute cardiac allograft rejection in mice. This process requires direct engagement of donor MHC class 11 molecules. That is, acute rejection by CD4(+) T cells requires target MHC class 11 expression by the donor and not by the host. However, it is unclear whether CD4(+) T cell rejection requires MHC class 11 expression on donor hemopoietic cells, nonhemopoietic cells, or both. To address this issue, bone marrow transplantation in mice was used to generate chimeric heart donors in which MHC class 11 was expressed either on somatic or on hemopoietic cells. We report that direct recognition of hemopoietic and nonhemopoietic cells are individually rate limiting for CD4(+) T cell-mediated rejection in vivo. Importantly, active immunization with MHC class II+ APCs triggered acute rejection of hearts expressing MHC class 11 only on the somatic compartment. Thus, donor somatic cells, including endothelial cells, are not sufficient to initiate acute rejection; but they are necessary as targets of direct alloreactive CD4 T cells. Taken together, results support a two-stage model in which donor passenger leukocytes are required to activate the CD4 response while direct interaction with the somatic compartment is necessary for the efferent phase of acute graft rejection.
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