Split tolerance induced by the intrathymic adoptive transfer of thymocyte stem cells

doi:10.1084/jem.168.1.143

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Split tolerance induced by the intrathymic adoptive transfer of thymocyte stem cells

RP Shimonkevitz and MJ Bevan
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

The intrathymic transfer of semiallogeneic CD4/CD8 double-negative (DN) thymocyte stem cells into irradiated host mice resulted in a transient state of chimerism in adoptive host thymus, spleen, and lymph nodes. Host-derived T cells, isolated from the thymus and periphery of the chimeric mice, were found to be specifically nonresponsive to the MHC antigens of the semiallogeneic DN donor in cytotoxicity assays. This nonresponsiveness was not permanent, but persisted as long as appreciable numbers of Thy-1 alloantigen-positive progeny of the DN donor cells could be detected in the spleen and lymph nodes of adoptive host mice. FACS sorting of DN donor cells before intrathymic transfer indicated that nonresponsiveness could be induced by Thy-1+ cells and was therefore not attributable to contaminating thymic macrophages, dendritic cells, or B cells. When FACS-sorted Thy-1+ (bm5 x bm12)F1 DN cells were transferred intrathymically into C57BL/6 hosts, nonresponsiveness to DN donor MHC class I but not class II alloantigen (split tolerance) was observed. These experiments were repeated using FACS-sorted Thy-1+ DN donor cells that were semiallogeneic to the irradiated adoptive host at either MHC class I or class II locus with similar results. Limiting dilution analysis showed that host-derived CTL precursors were tolerant of DN donor MHC class I alloantigen and no evidence for the involvement of suppressor T cells was found. The data indicate that murine thymocytes themselves are capable of tolerizing to MHC class I but not class II alloantigen after intrathymic transfer. The implications for intrathymic T cell differentiation and maintenance of self tolerance are discussed.
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Posselt, A., Barker, C., Tomaszewski, J., Markmann, J., Choti, M., Naji, A (1990). Induction of donor-specific unresponsiveness by intrathymic islet transplantation. Science 249: 1293-1295 [Abstract]
Webb, SR, Sprent, J (1990). Induction of neonatal tolerance to Mlsa antigens by CD8+ T cells. Science 248: 1643-1646 [Abstract]
Sprent, J, Gao, E., Webb, S. (1990). T cell reactivity to MHC molecules: immunity versus tolerance. Science 248: 1357-1363 [Abstract]
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Sprent, J., Gao, E.-K., Webb, S.R. (1989). T-cell Tolerance to H-2 Molecules: Role of the Thymus. Cold Spring Harb Symp Quant Biol 54: 789-797 [Abstract]