Decreased immunogenicity of fetal kidneys: The role of passenger leukocytes*

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Early in gestation, fetal rat kidneys are less immunogenic than in later fetal stages, and also less immunogenic than early-gestation fetal hepatic tissue. The purpose of this study was to test this observation in an allogeneic model, and to explore the basis of the decreased immunogenicity of early-gestation fetal kidneys. Kidneys were harvested from Fischer (FSH) fetal rats on the 15th, 17th, 18th, and 19th gestational day (GD), and then grafted under the kidney capsule of incompatible Wistar/Furth (W/F) adult male rats. Fetal hepatic tissue was harvested from 15th-GD FSH fetal rats, and then grafted under the kidney capsule of W/F adult male rats. Each recipient received either one kidney or a 3-mm piece of liver. Graft biopsies were obtained 10, 20, 30, and 40 days post-transplantation, and evaluated histologically. The severity of rejection was divided into three grades according to the degree of mononuclear infiltration and percentage of original fetal structures preserved. All fetal hepatic grafts were completely rejected (grade III) by the tenth posttransplantation day. In contrast, the degree of rejection of the kidneys was age-dependent. Fifteenth-GD kidneys showed a minimal or moderate degree of rejection (grade I or II) at 10, 20, and 30 days; however, 18th- and 19-GD kidneys were rejected (grade III) by the tenth post-transplantation day. To explore the basis for the decreased immunogenicity of 15th-GD kidneys, 20 adult W/F rats were divided into two groups. Each animal in the first group received one FSH 15th-GD kidney implanted under the kidney capsule. Animals in the second group received one FSH 15th-GD fetal kidney under the kidney capsule, and during the same operation, a piece of liver (5 mm in diameter) from the same fetal donor was implanted intraperitoneally. All animals were killed ten days post-transplantation. In animals receiving only fetal kidneys (nonchallenged group), 78% of the grafts showed grade I rejection and 22% showed grade II rejection. In recipients of both fetal tissues (challenged group), all the hepatic grafts recovered from the peritoneum were completely rejected (grade III). Of the kidney grafts, 64% showed grade III rejection and 36% showed grade II rejection. The difference between the challenged and nonchallenged groups was statistically significant (P<.001), and led us to speculate that early in gestation, the fetal liver contains dendritic cells (passenger luekocytes) that, acting as antigen-presenting cells, provide the two signals necessary for recipient lymphocyte activation. In contrast, 15th-GD kidneys express transplantation antigens (class I) but lack dendritic cells in their parenchyma, thus failing to produce an allogeneic reaction. The likeliness of this mechanism is supported by the observation that the recipient T lymphocytes, specifically activated by dendritic cells contained in fetal liver (being MHC-restricted), were able to recognize and reject antigens present on grafted 15th-GD kidneys. It is possible, later in gestation, for older fetal kidneys to become immunogenic as bone marrow-derived dendritic cells arrive in their parenchyma.

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*

Supported in part by Grant No. DK 32237 of the National Institutes of Health.

Presented at the 19th Annual Meeting of the American Pediatric Surgical Association, Tucson, Arizona, May 11–14, 1988.

1

From the Departments of Surgery and Anatomy, University of Minnesota, Minneapolis.

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