Document 0414
 DOCN  M9610414
 TI    Regulation by corticosteroids of Th1 and Th2 cytokine production in
       human CD4+ effector T cells generated from CD45RO- and CD45RO+ subsets.
 DT    9601
 AU    Brinkmann V; Kristofic C; Department of Asthma/Allergy Research,
       Ciba-Geigy Ltd., Basel,; Switzerland.
 SO    J Immunol. 1995 Oct 1;155(7):3322-8. Unique Identifier : AIDSLINE
       MED/96015975
 AB    Corticosteroids (CS) are widely used as immunosuppressive and
       anti-inflammatory agents, but their mechanism of action is not well
       understood. In this study we analyzed the effects of CS on the growth
       and differentiation of human CD4+45RO- naive and CD4+45RO+ memory T
       cells. To generate effector T cells secreting large amounts of Th1 and
       Th2 cytokines, FACS-sorted naive and memory subsets were primed and
       restimulated in vitro via the TCR in the presence of IL-2. CS added
       during priming reduced clonal expansion of both T cell populations, but
       the memory subset was 100-fold less sensitive. At lower concentrations,
       CS favored the development of effector T cells (from both subsets),
       which upon restimulation produced large amounts of the anti-inflammatory
       cytokine IL-10, but low amounts of IL-4, IL-5, or IFN-gamma.
       Interestingly, CS displayed different effects if it was added only
       during the restimulation of effector T cells. CS were unable to suppress
       clonal expansion of restimulated effector T cells. In effector T cells
       derived from the naive subset, CS induced production of IL-4 and IL-10,
       but blocked production of IL-5 and IFN-gamma. In effector T cells
       generated from the memory subset, CS blocked production of IL-4, IL-5,
       and IL-10, but inhibited production of IFN-gamma by only 50%, even if
       100-fold higher concentrations of CS were applied. These results
       indicate that persistent TCR stimulation, e.g., in chronic infection,
       may reduce the sensitivity of T cells to the antiproliferative effects
       of CS. Furthermore, the potential of CS to increase or suppress IL-4 and
       IL-10 production depending on the stage of T cell activation may explain
       in part the beneficial effects of CS in the treatment of acute
       inflammation and chronic allergic/asthmatic diseases.
 DE    Adrenal Cortex Hormones/*PHARMACOLOGY  Antigens, CD4/*IMMUNOLOGY
       Antigens, CD45/*IMMUNOLOGY  Cell Differentiation/DRUG EFFECTS  Cells,
       Cultured  Cytokines/*BIOSYNTHESIS  CD4-Positive T-Lymphocytes/DRUG
       EFFECTS/*IMMUNOLOGY  Human  Th1 Cells/IMMUNOLOGY  Th2 Cells/IMMUNOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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