GENETIC REQUIREMENTS FOR ACCELERATION OF DIABETES IN NONOBESE DIABETIC MICE EXPRESSING INTERLEUKIN-2 IN ISLET BETA-CELLS

被引：30

作者：

ALLISON, J ^{[1
]}

MCCLIVE, P ^{[1
]}

OXBROW, L ^{[1
]}

BAXTER, A ^{[1
]}

MORAHAN, G ^{[1
]}

MILLER, JFAP ^{[1
]}

机构：

[1] UNIV SYDNEY, CENTENARY INST CANC MED & CELL BIOL, SYDNEY, NSW 2006, AUSTRALIA

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 1994年 / 24卷 / 10期

关键词：

INTERLEUKIN-2 TRANSGENIC MICE; NONOBESE DIABETIC MICE; AUTOIMMUNITY; DIABETES SUSCEPTIBILITY GENES; CYTOKINES;

D O I：

10.1002/eji.1830241041

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Diabetes was dramatically accelerated in non-obese diabetic (NOD) transgenic mice that expressed interleukin-2 (IL-2) in their beta cells. A single cross to C57BL/6 completely prevented this effect and a further backcross to the NOD genetic background showed that at least two diabetes susceptibility loci (Idd1s and Idd3/10s) were required for the diabetes acceleration. T cells activated to islet antigens were not circulating in the mice. The accelerating effect of IL-2 was present, but decreased, in NOD mice that lacked CD8(+) T cells as well as in NOD SCID mice. The implications are that in the NOD genetic background, the production of cytokines, such as IL-2, by islet-specific CD4(+) T cells can lead to beta cell damage and diabetes and that CD8(+) T cells may have a role in accelerating diabetes onset.

引用

页码：2535 / 2541

页数：7

共 52 条

[1] CONSEQUENCES OF IN-SITU PRODUCTION OF IL-2 FOR ISLET-CELL DEATH [J].

ALLISON, J ;

OXBROW, L ;

MILLER, JFAP .

INTERNATIONAL IMMUNOLOGY, 1994, 6 (04) :541-549

[2] INFLAMMATION BUT NOT AUTOIMMUNITY OCCURS IN TRANSGENIC MICE EXPRESSING CONSTITUTIVE LEVELS OF INTERLEUKIN-2 IN ISLET BETA-CELLS [J].

ALLISON, J ;

MALCOLM, L ;

CHOSICH, N ;

MILLER, JFAP .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (05) :1115-1121

[3] GENETIC-BASIS FOR DIABETES RESISTANCE IN NOD WEHI MICE [J].

BAXTER, AG ;

HAMILTON, F ;

MANDEL, TE ;

AUGUSTINE, C ;

COOKE, A ;

MORAHAN, G .

EUROPEAN JOURNAL OF IMMUNOGENETICS, 1993, 20 (05) :409-417

[4] COMPARISON OF HIGH-DIABETES-INCIDENCE AND LOW-DIABETES-INCIDENCE NOD MOUSE STRAINS [J].

BAXTER, AG ;

ADAMS, MA ;

MANDEL, TE .

DIABETES, 1989, 38 (10) :1296-1300

[5] CD8 T-CELLS ARE NOT REQUIRED FOR ISLET DESTRUCTION INDUCED BY A CD4+ ISLET-SPECIFIC T-CELL CLONE [J].

BRADLEY, BJ ;

HASKINS, K ;

LAROSA, FG ;

LAFFERTY, KJ .

DIABETES, 1992, 41 (12) :1603-1608

[6]

CAMPBELL IL, 1994, AM J PATHOL, V145, P157

[7] NEUROLOGIC DISEASE INDUCED IN TRANSGENIC MICE BY CEREBRAL OVEREXPRESSION OF INTERLEUKIN-6 [J].

CAMPBELL, IL ;

ABRAHAM, CR ;

MASLIAH, E ;

KEMPER, P ;

INGLIS, JD ;

OLDSTONE, MBA ;

MUCKE, L .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :10061-10065

[8] ADOPTIVE TRANSFER OF DIABETES INTO IMMUNODEFICIENT NOD-SCID SCID MICE - RELATIVE CONTRIBUTIONS OF CD4+ AND CD8+ T-CELLS FROM DIABETIC VERSUS PREDIABETIC NOD.NON-THY-1A DONORS [J].

CHRISTIANSON, SW ;

SHULTZ, LD ;

LEITER, EH .

DIABETES, 1993, 42 (01) :44-55

[9]

COOKE A, 1990, CURR TOP MICROBIOL, V164, P125

[10]

DIETRICH W, 1992, GENETICS, V131, P423

← 1 2 3 4 5 6 →