Role of CD28/B7 costimulation in the dexamethasone-induced suppression of IFN-γ

被引:14
作者
Agarwal, SK [1 ]
Marshall, GD [1 ]
机构
[1] Univ Texas, Sch Med, Dept Internal Med, Div Clin Immunol & Allergy, Houston, TX 77030 USA
关键词
D O I
10.1089/10799900050198363
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vitro exposure of peripheral blood mononuclear cells (PBMC) to glucocorticoids (GC), at concentrations observed during psychologic stress, induces a shift in the human type 1/type 2 cytokine balance toward a type 2 cytokine response. The mechanisms involved in these cytokine alterations are unknown but likely include modulation of regulatory cytokines or the interaction between the antigen-presenting cell (APC) and T lymphocyte or both. The CD28/B7 costimulation pathway has been reported to modulate the type 1/type 2 cytokine balance and may contribute to the GC-associated cytokine alterations. Therefore, we sought to determine the effect of dexamethasone (Dex) on the expression and function of the human CD28/B7 costimulatory pathway and whether these alterations contribute to the Dex-induced type 1/type 2 cytokine alterations. Dex inhibited the expression of both CD80 and CD86 on THP-1 cells, a human acute monocytic leukemia cell line, as determined by flow cytometry. Dex also inhibited the expression of CD28 and CTLA-4 on phytohemagglutinin (PHA)-stimulated CD3(+) T lymphocytes, which was attenuated by the addition of interleukin-12 (IL-12). Lastly, activation of CD28 with anti-CD28 antibody attenuated the Dex-induced decrease in interferon-gamma (IFN-gamma) production by anti-CD3 antibody-stimulated PBMC. These data suggest that Dex induces a modulation of the CD28/B7 costimulatory pathway that contributes to the shift in the type 1/type 2 cytokine balance toward a predominant type 2 cytokine response.
引用
收藏
页码:927 / 934
页数:8
相关论文
共 38 条
[1]  
AAGARWAL SK, 1998, HUM IMMUNOL, V80, P707
[2]   Glucocorticoid-induced type 1 type 2 cytokine alterations in humans: A model for stress-related immune dysfunction [J].
Agarwal, SK ;
Marshall, GD .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1998, 18 (12) :1059-1068
[3]   β-adrenergic modulation of human type-1/type-2 cytokine balance [J].
Agarwal, SK ;
Marshall, GD .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 105 (01) :91-98
[4]  
Blotta MH, 1997, J IMMUNOL, V158, P5589
[5]   Differential modulation of B7-1 and B7-2 isoform expression on human monocytes by cytokines which influence the development of T helper cell phenotype [J].
Creery, WD ;
DiazMitoma, F ;
Filion, L ;
Kumar, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (06) :1273-1277
[6]   CONTRASTING EFFECTS OF GLUCOCORTICOIDS ON THE CAPACITY OF T-CELLS TO PRODUCE THE GROWTH-FACTORS INTERLEUKIN-2 AND INTERLEUKIN-4 [J].
DAYNES, RA ;
ARANEO, BA .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1989, 19 (12) :2319-2325
[7]  
DEKRUYFF RH, 1992, J IMMUNOL, V149, P3468
[8]   ALLERGEN EXPOSURE INDUCES THE ACTIVATION OF ALLERGEN-SPECIFIC TH2 CELLS IN THE AIRWAY MUCOSA OF PATIENTS WITH ALLERGIC RESPIRATORY DISORDERS [J].
DELPRETE, GF ;
DECARLI, M ;
DELIOS, MM ;
MAESTRELLI, P ;
RICCI, M ;
FABBRI, L ;
ROMAGNANI, S .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (07) :1445-1449
[9]  
Dubey C, 1996, J IMMUNOL, V157, P3280
[10]   Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells - Evidence for posttranscriptional regulation [J].
Fessler, BJ ;
Paliogianni, F ;
Hama, N ;
Balow, JE ;
Boumpas, DT .
TRANSPLANTATION, 1996, 62 (08) :1113-1118