Anti-CD3-Induced Anergy in Cloned Human Th 0, Th 1, and Th 2 Cells

Abstract

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 Th 1 but not Th 2 cell anergy. Furthermore, anti-CD3 induces anergy of Th 1- but not Th 2-type lymphokine secretion in Th 1 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 Th 0, Th 1, and Th 2 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-γ, and IL-4 secretion was determined to test for the anergic state. The initial anti-CD3 treatment induced cell proliferation, IL-2, IFN-γ, and/or IL-4 secretion by T cells of all three subsets which was followed by an anergic state in Th 0, Th 1, and Th 2 cells as shown by a 51 to >94% decrease in cell proliferation and IFN-γ 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 allergic 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 Th 2 cells can be anergized may be important for the development of new treatments in Th 2-mediated allergic disorders.