Glucocorticoid (GC) sensitivity and GC receptor expression differ in thymocyte subpopulations

被引:71
作者
Berki, T [1 ]
Pálinkás, L [1 ]
Boldizsár, F [1 ]
Németh, P [1 ]
机构
[1] Univ Pecs, Fac Med, Dept Immunol & Biotechnol, H-7643 Pecs, Hungary
关键词
Annexin V; anti-GCR mAb; apoptosis; dexamethasone; negative selection; positive selection; RU43044;
D O I
10.1093/intimm/14.5.463
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Positive and negative selection steps in the thymus prevent non-functional or harmful T cells from reaching the periphery. To examine the role of glucocorticoid (GC) hormone and its intracellular receptor (GCR) in thymocyte development we measured the GCR expression in different thymocyte subpopulations of BALB/c mice with or without previous dexamethasone (DX), anti-CD3 mAb, RU-486 and RU-43044 treatment. Four-color labeling of thymocytes allowed detection of surface CD4/CD8/CD69 expression in parallel with intracellular GCR molecules by flow cytometry. Double-positive (DP) CD4(+)CD8(+) thymocytes showed the lowest GCR expression compared to double-negative (DN) CD4(-)CD8(-) thymocytes and mature single-positive (SP) cells. DX treatment caused a concentration-dependent depletion of the DP cell population and increased appearance of mature SP cells with reduced GCR levels. GCR antagonists (RU-486 or RU-43044) did not influence the effect of DX on thymocyte composition; however, RU-43044 inhibited the high-dose GC-induced GCR down-regulation in SP and DN cells. GCR antagonists alone did not influence the maturation of thymocytes and receptor numbers. Combined low-dose anti-CD3 mAb and DX treatment caused an enhanced maturation (positive selection) of thymocytes followed by the elevation of CD69(+) DP cells. The sensitivity of DP thymocytes with a GCR(low)phenotype to GC action and the ineffectiveness of the GCR antagonist treatment may reflect a non-genomic GC action in the thymic selection steps.
引用
收藏
页码:463 / 469
页数:7
相关论文
共 38 条
  • [1] ANDERSON G, 1996, ANNU REV IMMUNOL, V14, P74
  • [2] Glucocorticoids in T cell development and function
    Ashwell, JD
    Lu, FWM
    Vacchio, MS
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 : 309 - 345
  • [3] Baus E, 1996, J IMMUNOL, V156, P4555
  • [4] Production and flow cytometric application of a monoclonal anti-glucocorticoid receptor antibody
    Berki, T
    Kumánovics, G
    Kumánovics, A
    Falus, A
    Ujhelyi, E
    Németh, P
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1998, 214 (1-2) : 19 - 27
  • [5] Equivalent doses and relative drug potencies for non-genomic glucocorticoid effects: A novel glucocorticoid hierarchy
    Buttgereit, F
    Brand, MD
    Burmester, GR
    [J]. BIOCHEMICAL PHARMACOLOGY, 1999, 58 (02) : 363 - 368
  • [6] Methylprednisolone inhibits uptake of Ca2+ and Na+ ions into concanavalin A-stimulated thymocytes
    Buttgereit, F
    Krauss, S
    Brand, MD
    [J]. BIOCHEMICAL JOURNAL, 1997, 326 : 329 - 332
  • [7] Dexamethasone-induced thymocyte apoptosis: Apoptotic signal involves the sequential activation of phosphoinositide-specific phospholipase C, acidic sphingomyelinase, and caspases
    Cifone, MG
    Migliorati, G
    Parroni, R
    Marchetti, C
    Millimaggi, D
    Santoni, A
    Riccardi, C
    [J]. BLOOD, 1999, 93 (07) : 2282 - 2296
  • [8] RAPID INVIVO EFFECTS OF GLUCOCORTICOIDS ON THE INTEGRITY OF RAT LYMPHOCYTE GENOMIC DEOXYRIBONUCLEIC-ACID
    COMPTON, MM
    CIDLOWSKI, JA
    [J]. ENDOCRINOLOGY, 1986, 118 (01) : 38 - 45
  • [9] USE OF RECEPTOR ANTIBODIES TO DEMONSTRATE MEMBRANE GLUCOCORTICOID RECEPTOR IN CELLS FROM HUMAN LEUKEMIC PATIENTS
    GAMETCHU, B
    WATSON, CS
    WU, SH
    [J]. FASEB JOURNAL, 1993, 7 (13) : 1283 - 1292
  • [10] Stress-free T-cell development: glucocorticoids are not obligatory
    Godfrey, DI
    Purton, JF
    Boyd, RL
    Cole, TJ
    [J]. IMMUNOLOGY TODAY, 2000, 21 (12): : 606 - 611