Increased expression of class I major histocompatibility complex antigens on hepatocytes in rejecting human liver allografts.

We studied hepatocellular expression of major histocompatibility (MHC) antigens in 43 serial liver transplant biopsies from 22 patients (42 percutaneous, 1 autopsy specimen), 4 normal liver biopsies, and 8 percutaneous biopsies of diseased livers from non-liver-transplant patients. Frozen tissue sections were stained by an indirect immunofluorescence technique using monoclonal antibodies (MCAb) that recognize nonpolymorphic human class I or class II MHC determinants. Ethidium bromide was used to stain nuclei and rhodamine-conjugated anti-basement-membrane antibodies to delineate epithelial and vascular structures. HLA-DR antigens recognized by MCAb OKIa1 and I2 were not detected on hepatocytes but were detected on the bile duct epithelium in 7 of 27 transplant biopsies, including 5 with acute rejection and 1 with chronic liver disease that later progressed to chronic rejection. HLA-A, B, C antigens recognized by MCAb 34/28 intensely stained cells lining the liver sinusoids but were negative on hepatocytes in 4 normal liver biopsies and 7 of 8 non-transplant biopsies. Expression of class I MHC antigens on hepatocyte membranes was increased in 17 of 21 (81%) biopsies from patients with acute rejection, in 4 of 4 with chronic transplant liver disease, but in only 3 of 18 (17%) biopsies from patients with no rejection (chi square = 8.62, P less than 0.01). Our observations demonstrate increased expression of MHC class I antigens in association with acute rejection in human orthotopic liver transplantation. Histologic resolution of the rejection episode is generally followed by a decrease in hepatocyte class I antigen expression. Further analysis of this response may have value in assessing the severity of the rejection and effectiveness of treatment.