Role of CD28/B7 costimulation in the dexamethasone-induced suppression of IFN-gamma.
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.
Agarwal
S K
SK
Division of Allergy and Clinical Immunology, The University of Texas-Houston Medical School, Houston, TX 77030, USA.
Marshall
G D
GD
D000069594:Abatacept; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism / Q000502:physiology*; D060908:CTLA-4 Antigen; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005938:Glucocorticoids; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D018664:Interleukin-12; D000069594:Abatacept; D003907:Dexamethasone; D007371:Interferon-gamma