Thymic education curtailed: defective immune responses in nude rats reconstituted with immature thymocyte subsets.
We have studied the ability of thymocyte subsets from allotype marked donors to populate athymic nude rats with T cells and to restore immune responsiveness. Following adoptive transfer, CD4-CD8- double-negative (DN) thymocytes (lymphoid precursor cells) or the CD4+CD8+ double-positive (DP) subset (intermediate thymocytes) or CD4+CD8- single-positive (CD4 SP) cells (mature thymocytes) each generated a permanent population of CD4+ progeny in syngeneic nude recipients. DN and DP thymocytes also produced small numbers of CD8+ cells; there was no evidence of 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 antibody responses] on nude rats that were almost indistinguishable from those conferred by mature peripheral recirculating CD4 T cells. Transfer of DP thymocytes extended the life-span of the immunoincompetent nudes and produced CD4+ progeny with near normal GVH responsiveness. However, DP-derived CD4+ cells were deficient at inducing allograft rejection and provided little or no help for antibody synthesis. The CD4+ progeny of DN thymocytes did not prolong the survival of nude recipients, gave reduced GVH reactivity, showed almost no capacity to initiate skin allograft rejection and failed to help B cells produce antibody. The results suggest that intrathymic development proceeds stepwise; each stage is accompanied by acquisition of additional properties that are reflected by T cell responses in the periphery. Thymic education does not become complete until the SP stage is reached when thymocytes become fully independent of the thymic microenvironment.
School of Biological Sciences, Medical School, University of Manchester, UK.
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CP
Yang
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EB
Bell
D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D015704:CD4 Antigens / Q000502:physiology; D002454:Cell Differentiation; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009026:Mortality; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D011923:Rats, Nude; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology*
D015704:CD4 Antigens