Endotoxin-induced gamma interferon production: contributing cell types and key regulatory factors

被引:112
作者
Varma, TK
Lin, CY
Toliver-Kinsky, TE
Sherwood, ER
机构
[1] Univ Texas, Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA
[2] Shriners Hosp Children, Galveston Burns Unit, Galveston, TX 77550 USA
关键词
D O I
10.1128/CDLI.9.3.530-543.2002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Gamma interferon (IFN-gamma) is an important mediator of endotoxin (lipopolysaccharide [LPS])-induced immune responses. However, the specific cell types that produce IFN-gamma in response to LPS and the cellular factors that regulate LPS-induced IFN-gamma production have not been fully determined. The present studies were undertaken to characterize the cell populations that produce IFN-gamma after LPS challenge in the spleens of mice and to determine the regulatory factors that modulate LPS-induced production of IFN-gamma. Our studies show that the levels of splenic IFN-gamma mRNA and protein production peak at 6 and 8 h, respectively, after systemic LPS challenge. Approximately 60% of IFN-gamma-producing cells are natural killer (NK) cells (CD3(-)DX5(+)) and 25% are NKT cells (CD3(+)DX5(+)). Most of the remaining IFN-gamma-producing cells are T cells (CD3(+)DX5(-)), macrophages, and dendritic cells. Functionally, interleukin-12 (IL-12) is the major IFN-gamma-stimulating factor after LPS challenge, with costimulation provided by IL-15, IL-18, and B7 proteins. IL-10 is a major inhibitor of LPS-induced IFN-gamma production. Unlike intact heat-killed gram-negative and gram-positive bacteria, the class II major histocompatibility complex did not play a functional role in LPS-induced IFN-gamma production. LPS is a potent stimulus for spienic IL-10, IL-12 p40, and IL-15 mRNA expression, whereas IL-12 p35 and IL-18 mRNAs, as well as B7 proteins, are constitutively expressed in the mouse spleen. Of the factors studied, IL-18 serves as the most potent costimulus with IL-12 for IFN-gamma production, followed by IL-15 and B7 proteins. These data demonstrate that NK cells and NKT cells are the most abundant IFN-gamma-producing cells in the mouse spleen after LPS challenge and that IL-10 and IL-12 are key functional regulators of LPS-induced IFN-gamma production.
引用
收藏
页码:530 / 543
页数:14
相关论文
共 41 条
[1]   Cellular responses to interferon-gamma [J].
Boehm, U ;
Klamp, T ;
Groot, M ;
Howard, JC .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :749-795
[2]   DEFINITIONS FOR SEPSIS AND ORGAN FAILURE AND GUIDELINES FOR THE USE OF INNOVATIVE THERAPIES IN SEPSIS [J].
BONE, RC ;
BALK, RA ;
CERRA, FB ;
DELLINGER, RP ;
FEIN, AM ;
KNAUS, WA ;
SCHEIN, RMH ;
SIBBALD, WJ .
CHEST, 1992, 101 (06) :1644-1655
[3]   Septic shock [J].
Butt, W .
PEDIATRIC CLINICS OF NORTH AMERICA, 2001, 48 (03) :601-+
[4]   Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro [J].
Carson, WE ;
Ross, ME ;
Baiocchi, RA ;
Marien, MJ ;
Boiani, N ;
Grabstein, K ;
Caligiuri, MA .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (06) :2578-2582
[5]  
Cauwels A, 1999, J IMMUNOL, V162, P4762
[6]  
Chang JT, 2000, EUR J IMMUNOL, V30, P1113, DOI 10.1002/(SICI)1521-4141(200004)30:4<1113::AID-IMMU1113>3.0.CO
[7]  
2-P
[8]   The expanding B7 superfamily: Increasing complexity in costimulatory signals regulating T cell function [J].
Coyle, AJ ;
Gutierrez-Ramos, JC .
NATURE IMMUNOLOGY, 2001, 2 (03) :203-209
[9]   Resistance of natural killer T cell-deficient mice to systemic Shwartzman reaction [J].
Dieli, F ;
Sireci, G ;
Russo, D ;
Taniguchi, M ;
Ivanyi, J ;
Fernandez, C ;
Troye-Blomberg, M ;
De Leo, G ;
Salerno, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (11) :1645-1651
[10]   Monocyte deactivation in septic patients: Restoration by IFN-gamma treatment [J].
Docke, WD ;
Randow, F ;
Syrbe, U ;
Krausch, D ;
Asadullah, K ;
Reinke, P ;
VolK, HD ;
Kox, W .
NATURE MEDICINE, 1997, 3 (06) :678-681