Differential infiltration by CD45RO and CD45RA subsets of T cells associated with human heart allograft rejection

Subsets of T cells express different isoforms of the leukocyte common antigen CD45; those expressing the glycoprotein 220 isoform (CD45RA) have been characterized as naive in their response to antigens, and those expressing the glycoprotein 180 isoform (CD45RO) as memory T cells. The association between the rejection status of human cardiac allograft recipients and the relative infiltration of the CD45 subsets of both CD8⁺ and CD4⁺ T cells was examined using two-color immunohistological labeling techniques on 33 heart transplant biopsies, categorized by routine histological and clinical criteria as mild (requiring no treatment) or moderate (requiring antirejection therapy) rejection. Double-labeling was performed using pairs of monoclonal antibodies to define the following populations: CD4⁺CD45RA⁺, CD4⁺CD45RO⁺, CD8⁺D45RA⁺, and CD8⁺-CD45RO⁺. The number of cells per high-power field (HPF) for each of these cell subsets was counted in every biopsy. In cases with mild rejection, infiltration was predominant for CD4⁺CD45RA⁺ cells (median = 5.0 cells/HPF) relative to CD4⁺CD45RO⁺ (3.12 cells/HPF), CD8⁺CD45RA⁺ (2.14 cells/HPF), and especially CD8⁺CD45RO⁺ (1.22 cells/HPF) populations. In cases with moderate rejection, all four subpopulations increased but were essentially equivalent in intensity, such that in comparison to cases with mild rejection, the smallest increase was seen for CD4⁺CD45RA⁺ cells (6.67 cells/HPF, P <0.09) and the greatest for CD8⁺CD45RO⁺ cells (7.00 cells/HPF, P <0.002). A majority of CD8 cells expressed CD45RA in 14 of 16 (88%) cases of mild rejection compared to only 2 of 17 cases of moderate rejection. Moreover, the ratio of CD45RO⁺ to CD45RA⁺ cells in each biopsy was higher in moderate versus mild rejection for both CD4 (median ratios = 1.13 versus 0.68, respectively; P <0.008) and CD8 (1.43 versus 0.58, respectively; P <0.005) subsets. A majority of T cells expressed CD45RO in cases of moderate rejection (11 of 14 or 79%), compared to only 1 of 13 (8%) cases of mild rejection. These findings indicate that during generally self-limited mild acute cardiac allograft rejection there is a predominance of naive CD45RA⁺ T cells, especially of the CD4 phenotype, whereas during moderate rejection there is a significant shift toward activated CD45RO⁺ T cells, especially in the CD8 population.