Absence of RT6+ T cells in diabetes-prone biobreeding/Worcester rats is due to genetic and cell developmental defects.
Diabetes-prone BB/Wor (DP) rats lack the RT6+ peripheral T cell subset whereas diabetes-resistant BB/Wor rats have normal numbers of RT6+ T cells. Lymphocyte transfusion experiments and in vivo depletion studies have demonstrated that RT6+ T cells have an important regulatory role in the pathogenesis of insulin-dependent diabetes mellitus in BB/Wor rats. In the present study, the results of genetic complementation studies indicate that the DP rat contains an intact RT6 gene, but fails to express the RT6.1 alloantigen in the functional absence of an accessory factor (provided by RT6+ cells). At the cellular level, irradiation chimeras demonstrate that the absence of RT6+ T cells in DP rats is due to an intrinsic defect that results in abnormal development and/or differentiation of prothymocytes into RT6+ T cells. The inability of DP prothymocytes to generate RT6+ T cells is not due to serum autoantibodies, lack of accessory cells, or to the presence of inhibitory cells. Inasmuch as DP bone marrow can transfer the susceptibility for diabetes to irradiated recipients, our present results suggest that an important predisposing factor for insulin-dependent diabetes mellitus in DP rats is the inability of DP prothymocytes to generate RT6+ T cells.
Angelillo
M
M
Department of Pathology, University of Connecticut Health Center, Farmington 06032.
Greiner
D L
DL
Mordes
J P
JP
Handler
E S
ES
Nakamura
N
N
McKeever
U
U
Rossini
A
A
D000818:Animals; D001323:Autoantibodies / Q000502:physiology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology; D007116:Immunization, Passive; D007519:Isoantigens / Q000235:genetics; D008213:Lymphocyte Activation; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB / Q000235:genetics*; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains / Q000235:genetics*; D011920:Rats, Inbred WF; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000528:radiation effects
D001323:Autoantibodies; D007519:Isoantigens