PRODUCTION OF HIGH-LEVELS OF TH1 AND TH2 CYTOKINES IN MICE WITH ACQUIRED TRANSPLANTATION TOLERANCE

Specific transplantation tolerance was induced in newborn mice by the intravenous injection of hematopoietic cells from semiallogeneic donor s. Success of tolerance induction was tested by skin allografts. Splee n cells from mice bearing tolerated allografts for more than 60 days a fter transplantation spontaneously produced high levels of various cyt okines. Production of both Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-10) cytokines, as well as of IL-3, was significantly increased in toleran t animals. The elevated production of Th1 cytokines was associated wit h the high secretory activity of CD4(+) cells, while the production of Th2 cytokines was high in both CD4(+) and CD8(+) cell populations. Th e hyperproduction of cytokines was an intrinsic property of the T cell s from tolerant animals and was not caused by a larger size of major T -cell subsets. The production of high levels of cytokines was a conseq uence of neonatal induction of tolerance and persisted for a long time after skin grafting of neonatally tolerized animals. These results sh ow that neonatal induction of transplantation tolerance results in the production of enhanced levels of Th1 and Th2 cytokines which could be involved in the establishment and maintenance of immunological tolera nce. (C) 1996 Academic Press, Inc.