PATTERNS OF GRAFT INFILTRATION AND CYTOKINE GENE-EXPRESSION DURING THE FIRST 10 DAYS OF KIDNEY-TRANSPLANTATION

Understanding of the events preceding acute cellular rejection of kidn ey transplants would be useful in the development of immunosuppressive strategies to prevent rejection. Information about these events in hu mans has been scarce, because of the lack of early, serial, biopsy sam ples. We took daily fine needle aspirates hom kidney allografts for th e first 10 days after transplant. Samples were analyzed by morphologic al cytology of graft-infiltrating cells, and reverse transcriptase-pol ymerase chain reaction for detection of interleukin (IL)-2, IL-4, IL-6 , IL-10, and gamma-interferon gene expression. During the first 4 days , all of the grafts developed a low-grade monocyte-rich mononuclear ce ll infiltrate, accompanied by IL-10 gene expression. Thereafter, the i nfiltrates either remained stable or intensified. Of the 13 grafts wit h dense infiltrates, seven developed graft dysfunction. The remaining six did not, despite significant interstitial infiltrates. Both reject ing and nonrejecting dense infiltrates were associated with a biphasic pattern of IL-2 and gamma-interferon gene expression, preceding and a ccompanying lymphocytic graft infiltration. Grafts that did not develo p dense infiltrates had no detectable IL-2 or gamma-interferon gene ex pression and did not suffer cellular rejection during the study period . The development of both rejecting and nonrejecting infiltrates was s trongly associated with DR mismatches between donor and recipient. IL- 2 and gamma-interferon gene expression are necessary, but not sufficie nt, for the development of acute cellular rejection in the first 10 da ys of kidney transplantation, and are more closely associated with the period leading up to rejection than with the period of graft dysfunct ion.