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J Thorac Cardiovasc Surg 1996;111:920-929
© 1996 Mosby, Inc.

CARDIAC AND PULMONARY REPLACEMENT

IN VITRO EVALUATION OF NEONATAL HUMAN IMMUNITY AGAINST THE PIG

From the Cardiac Transplantation Research Laboratory, Department of Surgery, Columbia University College of Physicians and Surgeons and the Cardiac Transplant Service, Division of Cardiothoracic Surgery, Columbia Presbyterian Medical Center, New York, N.Y.

Presented in part at the Sixty-seventh Scientific Sessions of the American Heart Association, Dallas, Tex., Nov. 14-17, 1994.

Received for publication Dec. 22, 1994 Accepted for publication July 3, 1995. Address for reprints: Robert E. Michler, MD, Director, Cardiac Transplant Service, and Director, Cardiac Transplantation Research Laboratory, Division of Cardiothoracic Surgery, Columbia Presbyterian Medical Center, 177 Fort Washington Ave., Milstein Hospital Building, Room 7435, New York, NY 10032.

Abstract

The critical shortage of organ donors has greatly limited the number of clinical allotransplantations. This is particularly true for neonatal patients, for whom xenotransplantation could provide an alternative therapeutic option to allotransplantation. The role of neonatal infant immunity in xenotransplantation is not, however, clearly understood. We examined both the proliferative responses of human neonatal lymphocytes to pig aortic endothelial cells and serum levels of neonatal natural antipig xenoantibody. Neonatal human lymphocytes and serum were isolated from umbilical cord blood. Adult human lymphocytes and serum were used as controls. A one-way xenogeneic mixed lymphocyte–endothelial cell reaction was performed, and lymphocyte proliferation was measured by tritiated thymidine uptake. Neonatal human lymphocytes recognized and proliferated in response to pig aortic endothelial cells (mean 63,926 ± 26,054 counts per minute). The level of xenogeneic mixed lymphocyte–endothelial cell reaction of neonatal lymphocytes was significantly lower (p < 0.004) than that of adult human lymphocytes (mean 122,444 ± 33,132 counts per minute). An enzyme-linked immunosorbent assay was performed to determine the binding of natural immunoglobulin M and G antibodies to pig endothelial cells. Whole-cell enzyme-linked immunosorbent assay demonstrated neonatal human serum to contain very low binding levels of natural antipig immunoglobulin M xenoantibody compared with adult serum. Like adult serum, neonatal human serum contained natural antipig immunoglobulin G xenoantibody. Neonatal serum was not cytotoxic to pig endothelial cells, suggesting that immunoglobulin G was not the predominant xenoreactive antibody. To assess whether neonatal pig endothelial cells also expressed xenoantigens, adult and neonatal cultured pig endothelial cells were examined by enzyme-linked immunosorbent assay with adult human serum. Adult human natural immunoglobulin M xenoantibody recognized not only adult pig endothelial cell xenoantigens but also neonatal pig endothelial cell xenoantigens. The binding levels of adult natural antipig immunoglobulin M xenoantibodies to adult and neonatal pig endothelial cells were similar, suggesting that neonatal pig aortic endothelial cells express xenoantigens. The findings of low binding levels of cytotoxic antipig immunoglobulin M xenoantibody and low levels of lymphocyte xenoreactivity to pig endothelial cells in human neonates suggests that pig organs may eventually be a suitable source of xenografts for human neonates. (J THORAC CARDIOVASC SURG 1996;111:920-9)

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