Differential expression of RANTES chemokine, TGF-beta, and leukocyte phenotype in acute cellular rejection and Quilty B lesions

Background: Because of the complexity of the trabeculated endocardial surfa ce and tangential histologic sectioning, the differentiation of acute cellu lar rejection (ACR) from Quilty B lesions (QB) in endomyocardial biopsies ( EMBs) is problematic. We hypothesized that the phenotype chemokine RANTES ( regulated upon activation, normal T cell expressed and secreted) expression of infiltrating cells and the pattern of expression of transforming growth factor-beta (TGF-beta) may distinguish ACR from QB. In previous studies, t he number of RANTES-positive cells and the expression of TGF-beta correlate d with the severity of rejection. Methods: We used immunohistochemical techniques to stain sections of human EMBs with only QB (n = 14) or with only ACR (International Society for Hear t and Lung Transplantation Grades 1A and 1B, n = 7; Grades 3A and 3B, n = 7 ) for B (CD20) and T-lymphocytes (CD3), macrophages (CD68), RANTES, and TGF -beta expression. We graded the percentage of positive cells from 0 to 4 (1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%, and 4 = 76% to 100%). Results: When ACR was compared with QB, we found no difference in the propo rtion of myocardial B cells (0.9 +/- 0.3 vs 1.1 +/- 0.3, p = 0.17); however , we found a lesser proportion of T cells (1.8 +/- 0.5 vs 2.8 +/-: 0.9, p < 0.01) but more macrophages (2.9 <plus/minus> 0.5 vs 1.1 +/- 0.6, p < 0.0001 ) in ACR than in QB. We also found more RANTES-positive leukocytes in ACR v s QB (2.8 <plus/minus> 1.3 vs 1.9 +/- 0.9, p = 0.03). In QB, many endocardi al vessels stained for TGF-beta (2.9 +/- 1.6). Myocardial vessels and injur ed myocytes in both ACR and QB expressed TGF-beta. Conclusions: In ACR, although T-lymphocytes are numerous, more than 50% of infiltrating cells are macrophages and more than 50% express RANTES. In QB lesions, more than 50% of infiltrating cells are T-lymphocytes and less tha t 50% of leukocytes will express RANTES. B cells are present in both ACR an d QB, but on average comprise only 25% of the cells present. Thus, a relati vely simple immunohistochemical analysis of endomyocardial biopsies may be useful in distinguishing ACR from QB.