Inhibition of IgE production and normalization of airways responsiveness by sensitized CD8 T cells in a mouse model of allergen-induced sensitization

Abstract

The functional role of CD8 T cells in in vivo IgE production, immediate cutaneous reactivity, and altered airways responsiveness (AR) was examined in a murine model of allergen-induced sensitization. Exposure of BALB/c mice to nebulized OVA triggered an IgE anti-OVA response in the serum, immediate-type skin test responses to OVA, and the development of increased AR (as measured by nonspecific reactivity to electrical field stimulation). In spleens of sensitized mice, analysis of the distribution of CD4/CD8 T cell subpopulations revealed an increase in total numbers of CD8 T cells. Transfer of purified spleen CD8 T cells from OVA-sensitized mice (CD8OVA) to sensitized recipients reduced serum IgE anti-OVA production by roughly 50%. Furthermore, studies of in vitro Ig production indicated that mononuclear cells from recipients of CD8 cells (CD8OVA > CD8PBS) produced less IgE and IgG1 antibodies, whereas in vitro IgG2a production was enhanced. The suppression of IgE production in recipients of CD8OVA T cells was associated with the failure to respond to intradermal challenge with OVA. The increase in AR found in sensitized mice was prevented after transfer of CD8OVA cells. When CD8 T cells from nonimmunized animals (CD8PBS) were used for the transfer into sensitized recipients, serum anti-OVA IgE was decreased by only 20%, whereas skin test reactivity and AR were not significantly affected. The ex vivo analysis of the pattern of cytokine-producing lymphocytes by immunofluorescence microscopy indicated that the sensitization procedure increased the fraction of IFN-gamma- and IL-4-positive cells in the spleen. Further in vitro analysis demonstrated that a high percentage of CD8 T cells were positive for IFN-gamma, whereas IL-4 was produced mainly by CD4 T cells. These data suggest that CD8 T cells may play an important role in the negative regulation of IgE production and AR and that IFN-gamma may be a relevant mediator of the functions of CD8 T cells in this model.