Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes.
To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC.
Suzuki
G
G
Division of Radiation Health, National Institute of Radiological Sciences, Chiba, Japan.
Moriyama
T
T
Takeuchi
Y
Y
Kawase
Y
Y
Habu
S
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D046508:Culture Techniques; D003849:Deoxyguanosine; D006183:H-2 Antigens / Q000276:immunology; D006239:Haplotypes; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000528:radiation effects; D008212:Lymphocyte Depletion; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011828:Radiation Chimera; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*
D006183:H-2 Antigens; D003849:Deoxyguanosine