Thymic education curtailed: defective immune responses in nude rats reconstituted with immature thymocyte subsets

We have studied the ability of thymocyte subsets from allotypemarked donors to populate athymlc nude rats with T cells andto restore immune responsiveness. Following adoptive transfer,CD4⁺CD8^– double-negative (DN) thymocytes (lymphold precursorcells) or the CD4⁺CD8⁺ double-positive (DP) subset (Intermediatethymocytes) or CD4⁺CD8^– single-positive (CD4 SP) cells(mature thymocytes) each generated a permanent population ofCD4⁺ progeny in syngeneic nude recipients. DN and DP thymocytesalso produced small numbers of CD8⁺ cells; there was no evidenceof a CD4^–CD8^– or CD4⁺CD8⁺ donor cell population.CD4 SP thymocytes conferred T cell functions graft-versus-host(GVH) responses, allograft rejection and thymus-dependent antibodyresponses] on nude rats that were almost indistinguishable fromthose conferred by mature peripheral recirculating CD4 T cells.Transfer of DP thymocytes extended the life-span of the immunolncompetentnudes and produced CD4⁺ progeny with near normal GVH responsiveness.However, DP-derived CD4⁺ cells were deficient at inducing allograftrejection and provided little or no help for antibody synthesis.The CD4⁺ progeny of DN thymocytes did not prolong the survivalof nude recipients, gave reduced GVH reactivity, showed almostno capacity to initiate skin allograft rejection and failedto help B cells produce antibody. The results suggest that intrathymicdevelopment proceeds stepwlse; each stage is accompanied byacquisition of additional properties that are reflected by Tcell responses in the periphery. Thymic education does not becomecomplete until the SP stage is reached when thymocytes becomefully independent of the thymic mlcroenvironment. Received 22 September 1993, accepted 22 December 1993.