ON THE ROLE OF INTERLEUKIN-10 IN THE INDUCTION AND MAINTENANCE OF SPECIFIC TRANSPLANTATION TOLERANCE

The role of a cytokine synthesis inhibitory factor, interleukin-10 (IL -10), in the induction and maintenance of neonatal transplantation tol erance was studied in mice. We showed that neonatal spleen cells (NSC) significantly inhibited interleukin-2 (IL-2) production by activated T cells from adult mice. Simultaneously we demonstrated a high express ion of the IL-10 gene in stimulated spleen cells from newborn mice. Ho wever, neutralizing monoclonal antibody (mAb) anti-IL-10 did not aboli sh the NSC-mediated suppression of IL-2 production. IL-10, therefore, does not appear to be the principal inhibitory molecule responsible fo r the suppression of IL-2 production. Similarly, specific alloantigen- activated spleen cells from adult tolerant animals were profoundly hyp oreactive in IL-2 production. This hyporeactivity was not reversed to a positive reactivity in the presence of mAb anti-IL-10. In addition, anti-IL-10 antibody enhanced proliferation in mixed lymphocyte culture s of cells from both control and tolerant animals, but the antibody di d not abrogate specific hyporeactivity of cells from tolerant mice. Th ese results thus showed that newborn animals were nonspecifically and tolerant animals specifically deficient in IL-2 production, but that I L-10 in neither case appeared to be responsible for this IL-2 hyporeac tivity.