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Organ-specific maturation of the major histocompatibility antigens in rats
Roman Metzger1, A Parasta, I Joppich
1Department of Pediatric Surgery, Dr. von Haunerschen Kinderspital, Klinikum Innenstadt, Ludwig-Maximilians-Universität, Munich, Germany. Roman.Metzger@kk-i.med.uni-muenchen.de
Abstract:
The essential role of major histocompatibility complex (MHC) class I and II in the process of rejection has been documented, and some studies suggest that fetal transplants could enjoy an organ-specific immunologic privilege. However, little is known as to when these antigens develop in fetal organs and which tissues mainly present them. This study investigated the dynamics of immunogenicity in the developing transplant organs of rats. The study focused on the classic transplant organs including lung, heart, liver, pancreas, intestine, and kidney. Fetal organs (14th and 20th day of gestation), organs at the 3rd, 7th, 10th, 14th and 28th days postpartum (pp), 2 and 3 months pp, and adult organs were taken and snap-frozen in liquid nitrogen. MHC expression was analyzed applying the APAAP technique on serial cryosections by two well-defined monoclonal antibodies (mAb) generated against rat MHC class I (Ox 18) and class II (Ox 6). Immunoreactivities were compared to those of different monoclonal markers against endothelial cells (HIS52, CD 31), histiocytes (ED 1, ED 2), dendritic cells (Ox-62), granulocytes (HIS48), B-cells (RLN-9D3), T-cells (Ox-52), CD 4 (Ox-35), CD 8 (Ox-8a), natural killer cells (10/78), and CD 45 (Ox-1, leukocyte common antigen). A non specific mAb (MR 12/53) served as a negative control. In all stages of organ maturation, MHC I expression was found predominantly on immunocompetent cells, endothelial cells, and certain parenchymal cells, whereas MHC II was almost entirely restricted to dendritic cells. In organ development, the onset of MHC I expression and the number of MHC II-positive cells varied in a time-dependent manner. However, between the 2nd and 3rd month pp the expression pattern was comparable to adult organs. The study indicates that each organ carries a variable immunologic burden, that matures heterogeneously. Consequently, the variable content of MHC I/II in organ maturation needs to be considered for any transplantation model.