Mechanisms of drug-induced lupus .3 Sex-specific differences in T cell homing may explain increased disease severity in female mice

被引:18
作者
Yung, R
Williams, R
Johnson, K
Phillips, C
Stoolman, L
Chang, S
Richardson, B
机构
[1] UNIV MICHIGAN, ANN ARBOR, MI 48109 USA
[2] ANN ARBOR VET ADM HOSP, ANN ARBOR, MI USA
来源
ARTHRITIS AND RHEUMATISM | 1997年 / 40卷 / 07期
关键词
D O I
10.1002/art.19
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To determine if sex-specific differences in lymphocyte trafficking could contribute to increased disease severity in female mice. Methods. A lupus-like disease was induced by injecting male and female mice with procainamide-treated T cell clones. Trafficking was examined by labeling the injected cells with Cr-51 or 5-chloromethylfluorescein diacetate. Results. Females developed more autoimmune liver disease and greater titers of anti-DNA antibodies than did males, and 2-7 times more cells accumulated in the female spleens. Splenectomy prevented the development of autoantibodies and renal and liver disease. Oophorectomy decreased the splenic homing, autoantibody titer, and liver disease severity, to levels found in males. Conclusion. T cells traffic differently to the spleen in male and female mice, and the spleen appears to be essential in the disease process. This suggests that differences in T cell homing could contribute to sex-specific disease severity in this murine model, and also possibly in human disease.
引用
收藏
页码:1334 / 1343
页数:10
相关论文
共 30 条
[1]   CRITICAL LOOK AT SPLENECTOMY-SLE CONTROVERSY [J].
BEST, WR ;
DARLING, DR .
MEDICAL CLINICS OF NORTH AMERICA, 1962, 46 (01) :19-+
[2]  
BURNET FM, 1965, AUSTRALAS ANN MED, V14, P185
[3]   ESTRADIOL ENHANCES LEUKOCYTE BINDING TO TUMOR-NECROSIS-FACTOR (TNF)-STIMULATED ENDOTHELIAL-CELLS VIA AN INCREASE IN TNF-INDUCED ADHESION MOLECULES E-SELECTIN, INTERCELLULAR-ADHESION MOLECULE TYPE-1, AND VASCULAR CELL-ADHESION MOLECULE TYPE-1 [J].
CID, MC ;
KLEINMAN, HK ;
GRANT, DS ;
SCHNAPER, HW ;
FAUCI, AS ;
HOFFMAN, GS .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (01) :17-25
[4]  
CUTOLO M, 1995, CLIN EXP RHEUMATOL, V13, P217
[5]   INTERACTIONS BETWEEN THE GONADAL-STEROIDS AND THE IMMUNE SYSTEM [J].
GROSSMAN, CJ .
SCIENCE, 1985, 227 (4684) :257-261
[6]  
GRUENBERG JC, 1986, AM SURGEON, V52, P366
[7]  
GUMKOWSKI F, 1987, BLOOD VESSELS, V24, P11
[8]  
HOCHBERG MC, 1993, EPIDEMIOLOGY SYSTEMI
[9]   STUDIES ON LYMPHOCYTE HOMING IN AUTOIMMUNE PRONE NZB MICE [J].
JUNG, LKL ;
GOOD, RA ;
FERNANDES, GA .
IMMUNOLOGICAL INVESTIGATIONS, 1986, 15 (01) :11-23
[10]   BOTH A MONOCLONAL-ANTIBODY AND ANTISERA SPECIFIC FOR DETERMINANTS UNIQUE TO INDIVIDUAL CLONED HELPER T-CELL LINES CAN SUBSTITUTE FOR ANTIGEN AND ANTIGEN-PRESENTING CELLS IN THE ACTIVATION OF T-CELLS [J].
KAYE, J ;
PORCELLI, S ;
TITE, J ;
JONES, B ;
JANEWAY, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1983, 158 (03) :836-856