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, we 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 donor antigen. Increased levels of donor CD4 and CD8 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.
Field
E H
EH
Department of Veterans Affairs Medical Center, Department of Medicine, University of Iowa College of Medicine, Iowa City 52246, U.S.A.
Rouse
T M
TM
Gao
Q
Q
Chang
B
B
D000818:Animals; D002678:Chimera / Q000276:immunology* / Q000528:radiation effects; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007519:Isoantigens / Q000008:administration & dosage; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000276:immunology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors
D016207:Cytokines; D007519:Isoantigens; D015847:Interleukin-4; D007371:Interferon-gamma