A Two-Step Model of Acute CD4 T-Cell Mediated Cardiac Allograft Rejection

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 II molecules. That is, acute rejection by CD4+ T cells requires target MHC class II expression by the donor and not by the host....

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-06, Vol.172 (12), p.7451-7458
Main Authors: Grazia, Todd J, Pietra, Biagio A, Johnson, Zachary A, Kelly, Brian P, Plenter, Robert J, Gill, Ronald G
Format: Article
Language:English
Subjects:
Acute Disease
Adoptive Transfer
Animals
Antigen-Presenting Cells - immunology
Antigen-Presenting Cells - transplantation
Bone Marrow Transplantation
CD4-Positive T-Lymphocytes - immunology
Endothelial Cells - immunology
Graft Rejection - immunology
Heart Transplantation - immunology
Histocompatibility Antigens Class II - analysis
Histocompatibility Antigens Class II - immunology
Mice
Mice, Knockout
Transplantation Chimera - immunology
Transplantation, Homologous
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Summary: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 II molecules. That is, acute rejection by CD4+ T cells requires target MHC class II expression by the donor and not by the host. However, it is unclear whether CD4+ T cell rejection requires MHC class II 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 II 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 II 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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.172.12.7451