Cyclosporine microemulsion- and mycophenolate mofetil-related lymphoid aggregates are not associated with acute rejection

Background. Microemulsion cyclosporine, mycophenolate mofetil, and predniso ne have become a common immunosuppressive protocol in renal transplantation . We identified lymphocytic infiltrates in transplant fine-needle aspirates and core biopsies from patients on this regimen without acute rejection cl inically or by standardized morphological criteria and investigated this in flammatory response. Methods. Twenty-eight aspirates from 21 patients were included and assessed in the standard fashion. Nine core biopsies showing interstitial lymphocyt ic infiltration were evaluated with antibodies against CD3, CD4, CD8, CD20, CD30, CD56, KP1, and epithelial membrane antigen (EMA). Aspirates and biop sies were assessed for tubular cell major histocompatibility complex (MHC) class II antigen and for gamma -interferon (gamma -IFN), interleukin-4 (IL- 4), and IL-10 mRNAs by reverse transcription-polymerase chain reaction. Results. Fifteen aspirates showed immune activation solely due to mature ly mphocytes and monocytes; 13 had no immune activation. All aspirates were ne gative for MHC class II antigens. Of 6 activated aspirates assessed for gam ma -IFN m-RNA, 5 were negative. All 21 patients had similar clinical charac teristics and recovered renal function without rejection treatment. The cor e biopsies had lymphocytes in 5-30% of the interstitium. The cells were 70- 85% CD3+, with 50-85% CD4+, 3-10% KP1+, and rare cells CD56+. No T-cell act ivation was present (EMA- and CD30-). Seven biopsies were assessed and were negative for gamma -IFN mRNA; only one biopsy had weakly positive MHC clas s II staining. Two activated aspirates were negative for IL-4 and IL-10 mRN A, while three biopsies each contained IL-4 and IL-10 mRNAs. Conclusions. Inactive interstitial lymphoid infiltrates are frequent in pat ients on this drug regimen and should not be interpreted as acute rejection , particularly in aspirate samples. These lymphocytes may play a role in lo ng-term allograft acceptance.