Background and purpose: NK antigens define a unique subpopulation of lymphocytes that include both NK and T cells capable of secreting cytokines as early as 30 min after stimulation. The purpose of this study was to investigate the mechanism of antibody-induced deletion of NK1.1+ lymphocytes in vivo. Materials and methods: Studies were done in various strains and genetically altered mice. After Mab antibody treatment or sensitization, lymphocytes were removed from the mice and stained for analysis of intracellular cytokines, identifying surface markers, and apoptosis by flow cytometry. Results: We observed that while remaining resistant to Mab treatment themselves, T cells with NK1.1+ antigens biased the mechanism of antibody mediated depletion of the NK1.1+ NK cells in vivo towards apoptosis. Furthermore the resistant NK1.1+ T cells were stimulated by the in vivo antibody treatment to produce IL-4. Experiments with genetically altered or deficient mice suggested that IL-4 from the NK1.1+ T cell was essential for the efficiency of antibody mediated apoptosis. The possibility was raised that the NK1.1+ may use apoptosis to downregulate the NK1.1+ NK cells, thus preventing early enhancement of Th1 type responses. In support of this postulate, we observed an increase in the number of NK1.1+ T cells synthesizing IL-4 in the lungs of mice challenged locally with ovalbumin, an antigen known to induce Th2 responses. In contrast, we saw no increase in NK1.1+ T cells and the presence of increased IFN-γ producing NK cells in lungs of mice challenged intratracheally with Bleomycin, a known inducer of inflammation (Th1). Conclusions: NK1.1+ T cells resist depletion by anti-NK1.1 Mab and participate in the antibody mediated apoptosis of NK cells. The two subpopulations of lymphocytes expressing NK antigens may create the cytokine microenvironment for initiating and maintaining Th1 or Th2 responses in the lung and may regulate each other by apoptosis.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Dec 1 1996|
- Immune regulation
- NK1.1 cells
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)