THE EFFECT OF CYCLOPHOSPHAMIDE TREATMENT ON LYMPHOCYTE SUBSETS IN THE NONOBESE DIABETIC MOUSE - A COMPARISON OF VARIOUS LYMPHOID ORGANS

被引:21
作者
ZHANG, ZL [1 ]
GEORGIOU, HM [1 ]
MANDEL, TE [1 ]
机构
[1] ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,TRANSPLANTAT UNIT,PO ROYAL MELBOURNE HOSP,PARKVILLE,VIC 3050,AUSTRALIA
关键词
NONOBESE; DIABETIC MOUSE; INSULIN DEPENDENT DIABETES-MELLITUS; AUTOIMMUNITY; CYCLOPHOSPHAMIDE; LYMPHOCYTE SUBSETS;
D O I
10.3109/08916939309004833
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The nonobese diabetic (NOD) mouse is a model for human Type 1 diabetes mellitus. Pancreatic beta-cell destruction in NOD mice is mediated by an autoimmune process which can be accelerated by cyclophosphamide (CP). We studied the phenotype of lymphocytes from central, peripheral and regional lymphoid tissues in prediabetic NOD and C3H mice before and after a single large dose of CP. All lymphoid organs showed a greatly diminished cell number and most alterations appeared early after CP and were transient, but an aggressive insulitis was not seen in NOD mice until 14 d after injection. The pancreatic islets in C3H mice remained intact and were not infiltrated. NOD female mice, which are most prone to spontaneous and CP-induced diabetes, exhibited the most unusual lymphoid kinetics after treatment with CP. Their thymus and spleen showed the least relative drop in total cell number and the most rapid rate of recovery. The thymus of these mice was also found to have an increased proportion of CD3+ thymocytes while CD4/CD8 double positive thymocytes decreased 7 d after CP. At 14 d after CP the number of IL-2R+ thymocytes had surpassed that of normal levels. The most dramatic observation was the rapid recovery and overshoot in the number of pancreatic lymph node cells of female NOD mice which coincided with aggressive insulitis.
引用
收藏
页码:1 / 10
页数:10
相关论文
共 22 条
[1]  
Makino S., Kunimoto K., Muraoka T., Mizushima Y., Katagiri K., Tochino Y., Breeding of a non-obese, diabetic strain of mouse, Experimental Animals, 29, pp. 1-13, (1980)
[2]  
Fujita T., Yui R., Kusumoto Y., Serizawa Y., Makino S., Tochino Y., Lymphocytic insulitis in a non-obese diabetic (NOD) strain of mice: An immunohistochemical and electron microscope investigation, Biomed Res, 3, pp. 429-443, (1982)
[3]  
Pontcsilli O., Carotenuto P., Gazda L.S., Pratt P.F., Prowse S.J., Circulating lymphocyte populations and autoantibodies in nonobese diabetic (NOD) mice: A longitudinal study, Clin Exp Immunol, 70, pp. 84-93, (1987)
[4]  
Reddy S., Bobby N.J., Elliott R.B., Ontogeny of islet cell antibodies, insulin autoantibodies and insulitis in the non-obese diabetic mouse, Diabeiologia, 31, pp. 322-328, (1988)
[5]  
Atkinson M.A., Maclaren N.K., Autoantibodies in nonobese diabetic mice immunoprecipitate 64,000-M, islet antigen, Diabetes, 37, pp. 1587-1590, (1988)
[6]  
Harada M., Makino S., Promotion of spontaneous diabetes in non-obese diabetic-prone mice by cyclophosphamide, Diabetologia, 27, pp. 604-606, (1984)
[7]  
Yasunami R., Bach J.-F., Anti-suppressor effect of cyclophosphamide on the development of spontaneous diabetes in NOD mice, Eur J Immunol, 18, pp. 481-484, (1988)
[8]  
Charlton B., Bacelj A., Slattery R.M., Mandel T.E., Cyclophosphamide-induced diabetes in NOD/Wehi mice: Evidence for suppression in spontaneous autoimmune diabetes mellitus, Diabetes, 38, pp. 441-447, (1989)
[9]  
Charlton B., Mandel T.E., Progression from insulitis to β-cell destruction in NOD mouse requires L3T4<sup>+</sup> T-lymphocytes, Diabetes, 37, pp. 1108-1112, (1988)
[10]  
Charlton B., Bacelj A., Mandel T.E., Administration of silica particles or anti-Lyt2 antibody prevents β-cell destruction in NOD mice given cyclophosphamide, Diabetes, 37, pp. 930-935, (1988)