Functional maturation of recent thymic emigrants in the periphery: development of alloreactivity correlates with the cyclic expression of CD45RC isoforms.
The transition from fully developed CD4+CD8- single-positive (SP) thymocytes into fully mature recirculating peripheral T cells is both poorly understood with regard to the expression of restricted isoforms (CD45R) of the leukocyte common antigen and in terms of T cell function. The present investigation monitored the extrathymic development of CD4+CD8- SP thymocytes in euthymic recipients using allotype-marked donor cells and monoclonal antibody OX22 which recognizes an epitope on the C exon of rat CD45R. We established that donor-derived cells in the blood 1 day later bore the phenotype of the injected SP thymocytes (CD4+ Thy-1+ CD45RC-). T cells with the identical phenotype were also present in the thoracic duct lymph of uninjected rats, suggesting that the Thy-1+ CD45RC- T cells represent recent thymic emigrants (RTE) which have migrated to the periphery of their own accord. During extrathymic maturation donor-derived peripheral RTE lost Thy-1 within 3 days and expressed the CD45RC+ high molecular weight isoform by day 7; between days 8 and 14 a proportion (25%-30%) of the donor cells once again lost the high molecular weight isoform (CD45RC-). The transition of SP (CD45RC-) thymocytes to fully mature CD45RC+ CD4 T cells via intermediate peripheral RTE was accompanied at each stage by an increased ability of the maturing T cells to induce skin allograft rejection. Unexpectedly, the subsequent loss of the high molecular weight isoform, following presumed antigen encounter, was associated with a significant reduction in the ability of this Thy-1-CD45RC- subpopulation to effect graft rejection. The cyclic expression of CD45RC isoforms on both immature and mature CD4 T cells and the fact that the low molecular weight isoform was found in the periphery on both RTE (unquestionably naive) and antigen-experienced CD4 T cells, makes it unlikely that this isoform uniquely identifies memory T cells, at least in the rat.
Immunology Research Group, Cell and Structural Biology, Medical School, University of Manchester, GB.
C P
CP
Yang
E B
EB
Bell
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016827:CD8 Antigens / Q000032:analysis; D002465:Cell Movement; D006084:Graft Rejection; D006649:Histocompatibility Antigens / Q000032:analysis*; D017493:Leukocyte Common Antigens; D008562:Membrane Glycoproteins / Q000032:analysis; D051381:Rats; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000502:physiology*; D018800:Thy-1 Antigens
D015703:Antigens, CD; D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D017493:Leukocyte Common Antigens