Association between enhanced Th2/Th1 cytokine profile and donor T-cell chimerism following total lymphoid irradiation

Total lymphoid irradiated (TLI) mice develop antigen specific tolerance if the initial antigen exposure occurs shortly after the completion of TLI. We injected TLI-treated mice with semiallogeneic donor cells at 2, 7, or 28 days after completing TLI and determined the levels of donor CD4 and CD8 cells 5 to 7 weeks after TLI treatment, The level of chimerism correlated with the timing of the initial alloantigen exposure. Donor CD4 and CD8 cells were noted only in day 2 or 7 injected mice. Because donor cell chimerism suggested increased in vivo survival of donor cells, Ne used the level of donor cell chimerism as a surrogate marker for tolerance to examine the relationship between the development of tolerance and enhanced Th2/Th1 cytokine responses to doctor antigen, Increased levels of donor CD4 and CDS cells in the TLI-treated mice was associated with increased Th2/Th1 cytokine production and decreased CTL activity to donor antigen in vitro. Higher Th2/Th1 cytokine levels also correlated with lower CTL activity, The results indicate that the increased production of Th2/Th1 may function to enhance survival of donor cells in TLI-treated mice and suggest that tolerance induction after TLI treatment involves immunoredirection. (C) American Society for Histocompatibility and Immunogenetics, 1997.