Development of grafted gld cells in athymic and euthymic recipients.
Mice homozygous for the gld (generalized lymphoproliferative disease) and lpr (lymphoproliferation) mutations display similar autoimmune and lymphoproliferative diseases. Both result from defective apoptosis, the targets of the lpr and gld mutations being the genes for, respectively, an apoptosis-signalling receptor [the Fas antigen receptor (FasR)] and its counter-receptor [the Fas ligand (FasL)]. Though this definitely causes the development and accumulation of large numbers of unusual Thy-1+ B220+ cells in peripheral lymphoid organs, details on how this actually occurs are still lacking. Whether differentiation of gld T cells into Thy-1+ B220+ cells might depend on the environment was analysed by phenotyping the cells which expanded in four different immunodeficient environments (nubg, nulpr, scid and scidbg). Though all four types of congenic chimeras developed hyperglobulinaemia, autoimmunity and a lymphoproliferative disease, substantial differences were found for the athymic and euthymic chimeras. In the athymic gld chimeras, the lymphoproliferation concerned all cell subsets, whereas in the euthymic gld chimeras it was, as in gld mice, due to the accumulation of cells of the Thy-1+ B220+ subset. Thus, the gld T cells could proliferate without differentiating into the Thy-1+ B220+ subset, but this depended on the nature of the environment. Furthermore, emergence of a gld syndrome in these four environments would suggest that B cells and stromal cells do not express FasL, at least in levels sufficient to compensate for the deficiency of the grafted gld cells.
Rosenblatt
N
N
Laboratoire d'Immunologie, Université de Strasbourg, France.
Hartmann
K U
KU
Loor
F
F
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D007136:Immunoglobulins / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D018800:Thy-1 Antigens / Q000032:analysis; D013950:Thymus Gland / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology
D007136:Immunoglobulins; D018800:Thy-1 Antigens