Anti-CD3-induced anergy in cloned human Th0, Th1, and Th2 cells.
In the mouse, activation of T cells by T cell receptor (TCR) crosslinking with anti-CD3 antibodies in the absence of a costimulatory signal induces Th1 but not Th2 cell anergy. Furthermore, anti-CD3 induces anergy of Th1- but not Th2-type lymphokine secretion in Th0 cells. This study was designed to determine whether this is also the case in man. Human rye grass allergen Lol p I-specific cloned CD4+ T helper cells of subtypes Th0, Th1, and Th2 were treated with immobilized anti-CD3. The cells were rested for 4 days and then activated under optimal conditions with antigen and antigen-presenting cells (APCs). Cell proliferation and IL-2, IFN-gamma, and IL-4 secretion was determined to test for the anergic state. The initial anti-CD3 treatment induced cell proliferation, IL-2, IFN-gamma, and/or IL-4 secretion by T cells of all three subsets which was followed by an anergic state in Th0, Th1, and Th2 cells as shown by a 51 to > 94% decrease in cell proliferation and IFN-gamma and/or IL-4 secretion after subsequent APC and Lol p I activation. Addition of IL-2 or IL-4 during anti-CD3 treatment of the cells did not prevent unresponsiveness. However, the addition of IL-2 but not IL-4 during APC and Lol p I stimulation partially reversed the anergic state. These data demonstrate that, contrary to the mouse, cloned T cells of all three human T helper cell subtypes are anergized by anti-CD3 TCR activation in the absence of costimulatory signals. The fact that human Th2 cells can be anergized may be important for the development of new treatments in Th2-mediated allergic disorders.
Nguyen
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DD
Department of Pediatrics, University of California at San Diego, School of Medicine, La Jolla 92093, USA.
Beck
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Spiegelberg
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HL
D000485:Allergens / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D052179:Antigens, Plant; D017252:CD3 Complex / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D002999:Clone Cells; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis / Q000502:physiology; D007376:Interleukin-2 / Q000032:analysis / Q000502:physiology; D015847:Interleukin-4 / Q000032:analysis / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008222:Lymphokines / Q000032:analysis / Q000502:physiology; D010940:Plant Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D052179:Antigens, Plant; D017252:CD3 Complex; D007376:Interleukin-2; C042814:Lol p I protein, Lolium perenne; D008222:Lymphokines; D010940:Plant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma