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.
Yang
C P
CP
School of Biological Sciences, Medical School, University of Manchester, UK.
Bell
E B
EB
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