Discriminating rejection from CMV infection in renal allograft recipients using flow cytometry

The ability to distinguish among rejection, cytomegalovirus (CMV) infection, and cyclosporin toxicity in the symptomatic renal allograft recipient remains one of the major issues in clinical transplantation. The practical application of immunologic monitoring of peripheral blood lymphocytes through the use of fluorescently labeled monoclonal antibodies and single-color flow cytometry has been limited by the inability to demonstrate significant correlations between the levels of specific T-cell subset populations and the cause of impaired renal function. In the present study using two-color analysis, we monitored the expression of interleukin-2 receptor (IL-2R) and HLA-DR antigen on the T-cells of a group of 51 renal cadaveric allograft recipients receiving cyclosporin, azathioprine, and prednisone for an average of 4 months after transplantation. We found that the proportion of CD3+ cells coexpressing IL-2R increased above baseline during 12 out of 14 rejection episodes that took place during the course of the study (P less than 10(-6)). Alternatively, we found that the proportion of cells coexpressing HLA-DR antigen on CD2+ cells increased above baseline during 11 out of 11 CMV infections (P less than 10(-6)). There was no correlation between the level of IL-2R+CD3+ cells and CMV infection or between the level of CD2+DR+ cells and rejection. These relationships showed a high degree of sensitivity and specificity when used to discriminate among possible etiologies for decreased renal function in the symptomatic patient.