Major histocompatibility complex (MHC) class II restriction, lymphokine production, and IgE regulation of house dust mite-specific T-cell clones.

To elucidate the regulatory mechanism of human IgE synthesis, we have cloned house dust mite (Dermatophagoides pteronyssinus; Dp)-specific T-cell clones from three asthmatic children and three healthy individuals. Twelve clones were cloned from each group. All of these clones were CD3+, CD4+, CD8-, and HLA-DR+. After stimulation with allergen in the presence of antigen presenting cells (APCs), half of the T-cell clones from asthmatic children and one-third of those from normals produced interleukin 4 (IL-4). None of the patients' clones produced interferon gamma (IFN-gamma), while 10 of 12 normals' clones did. After stimulation with calcium ionophore A23187 and phorbol myristic acetate (PMA), the production of IL-4 was markedly increased in both patients and normals. However, only 3 of the 12 patients' clones produced IFN-gamma, while all of the normals' clones did. The T-cell clones of both patients and normals produced comparable IL-2. To study the kinetics of lymphokine productions, a HLA-DRw12-restricted T-cell clone (FYD 3.1) was stimulated, respectively, with a combination of A23187 and PMA, phytohemagglutinin (PHA), or Dp antigen in the presence of APCs. Maximal IL-2 and IL-4 productions were detected 12 hr after A23187 and PMA stimulation, whereas IFN-gamma could not be detected even 36 hr after stimulation. When stimulated with PHA, the production of IFN-gamma peaked on the fourth day, but IL-4 was not detected. After stimulation with Dp antigen and APCs, IL-4 and IL-2 were detected on the second and third days, but IFN-gamma was not detected. The IgE production by autologous purified B cells in the presence of allergen or IL-4 was found to be augmented by the FYD 3.1 T-cell clones. IFN-gamma was observed to counteract the effects of the T-cell clones and IL-4. Thus, the secretory patterns of lymphokine and kinetics of lymphokine production of allergen-specific T-cell clones can be used to explore the regulatory mechanism of human IgE synthesis [corrected].