DETAILED ANALYSIS AND DEMONSTRATION OF DIFFERENCES IN THE KINETICS OF INDUCTION OF CLASS I AND CLASS II MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS IN REJECTING CARDIAC AND KIDNEY ALLOGRAFTS IN THE RAT

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Abstract
In this paper, we analyze in detail donor class I and class II major histocompatibility complex (MHC) antigen induction in heart and kidney allografts in the DA-to-PVG rat strain combination. The immunohistological techniques and quantitative absorption analyses utilize monoclonal antibodies and assay systems specific for donor class I and class II MHC antigens, to enable precise interpretation of the results in terms of the MHC antigens of the graft. Quantitative absorption analyses were performed on homogenates comprising 4–6 allografts pooled at each interval examined (days 1–5 for kidneys, days 3–7 for hearts). In the heart allografts, donor class I antigen induction begins at day 3 after transplantation and proceeds rapidly on the 4th and 5th postoperative days. The maximum level (a 10-fold increase in comparison with normal heart) occurs at day 6, and thereafter the level declines. Donor class II antigen induction in the heart allografts follows a similar pattern. In kidney allografts, it was of particular interest that donor class I induction occurred much more rapidly, being already evident on the first postoperative day, and reaching levels 20-fold greater than normal kidney by day 3. Maximum levels (approximately 30-fold that of normal kidney) of donor class I antigens were reached on days 4 and 5. Donor class II induction, by contrast, developed in kidney grafts with kinetics similar to that seen for class II induction in heart grafts (beginning at day 3 and reaching a maximum of 7-fold over normal kidney at day 5). Immunohistological studies were performed at days 1, 3, 5, and 7 after transplantation. These confirmed the early induction of donor class I antigen in the kidney allografts. In kidney, by the fifth postoperative day, all tubules in the cortex and medulla, and the arteriolar vascular endothelium, were strongly positive for class II antigens. However, the glomerulus, including the glomerular capillary endothelium, remained donor-class-II-negative, except for induction of class II antigens on Bowman's capsule. The endothelium of interstitial capillaries also probably remained class-II-negative. These results have potentially important implications for understanding the development of the rejection response.

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