INHIBITION OF IGE PRODUCTION AND NORMALIZATION OF AIRWAYS RESPONSIVENESS BY SENSITIZED CD8 T-CELLS IN A MOUSE MODEL OF ALLERGEN-INDUCED SENSITIZATION

The functional role of CD8 T cells in in vivo IgE production, immediat e cutaneous reactivity, and altered airways responsiveness (AR) was ex amined in a murine model of allergen-induced sensitization. Exposure o f BALB/c mice to nebulized OVA triggered an IgE anti-OVA response in t he serum, immediate-type skin test responses to OVA, and the developme nt of increased AR (as measured by nonspecific reactivity to electrica l field stimulation). In spleens of sensitized mice, analysis of the d istribution of CD4/CD8 T cell subpopulations revealed an increase in t otal numbers of CD8 T cells. Transfer of purified spleen CD8 T cells f rom OVA-sensitized mice (CD8OVA) to sensitized recipients reduced seru m IgE anti-OVA production by roughly 50%. Furthermore, studies of in v itro Ig production indicated that mononuclear cells from recipients of CD8 cells (CD8OVA > CD8PBS) produced less IgE and IgG1 antibodies, wh ereas in vitro IgG2a production was enhanced. The suppression of IgE p roduction in recipients of CD8OVA T cells was associated with the fail ure to respond to intradermal challenge with OVA. The increase in AR f ound 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 significantl y affected. The ex vivo analysis of the pattern of cytokine-producing lymphocytes by immunofluorescence microscopy indicated that the sensit ization procedure increased the fraction of IFN-gamma- and IL-4-positi ve 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 c ells may play an important role in the negative regulation of IgE prod uction and AR and that IFN-gamma may be a relevant mediator of the fun ctions of CD8 T cells in this model.