CD8+ T-cells are required for adoptive transfer of the BB rat diabetic syndrome.
LGLs with NK activity account for the majority of BB rat PBLs expressing CD8, and it has been suggested that these LGL/NK cells are involved in the pathogenesis of the BB rat diabetic syndrome. By using a recently developed mouse MoAb, 3.2.3, specific for rat LGL, we demonstrate that BB and WF rat LGLs are phenotypically and functionally similar. To directly assess the role of LGLs in the development of diabetes in vivo, an adoptive transfer of T-cells to young LGL/NK cell-depleted diabetes-prone BB rats was performed. CD4+8- and CD4-8+ T-cells (> 98.5% pure), isolated from diabetic BB rats, were activated in vitro and injected into 30-day-old diabetes-prone BB rats. Recipients were either chronically injected with 3.2.3 (n = 15) or received an isotype-matched irrelevant MoAB (n = 14). Secondary lymphoid organs of 3.2.3-treated recipients contained < 0.1% 3.2.3+ lymphocytes, and this depletion was associated with a major decrease in the NK activity of their splenocytes. Despite this, the incidence of diabetes in 3.2.3-treated animals (40%) was not significantly different from that observed in control recipients (57%). Thus, the BB rat diabetic syndrome can be adoptively transferred in the absence of LGL/NK cells, suggesting that BB rat CD8+ T-cells are involved in the diabetogenic process. To assess the pathogenic role of CD8+ T-cells, we compared the incidence of diabetes in three groups of diabetes-prone BB recipients after injection of T-cells isolated from diabetic donors.(ABSTRACT TRUNCATED AT 250 WORDS)
Edouard
P
P
McGill Nutrition and Food Science Center, Department of Medicine, McGill University, Montreal, Canada.
Hiserodt
J C
JC
Plamondon
C
C
Poussier
P
P
D000818:Animals; D000911:Antibodies, Monoclonal; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive; D008297:Male; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB; D011920:Rats, Inbred WF; D013577:Syndrome; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology* / Q000637:transplantation
D000911:Antibodies, Monoclonal