OVALBUMIN-SPECIFIC, MHC CLASS I-RESTRICTED, ALPHA-BETA-POSITIVE, TC1 AND TC0 CD8(-CELL CLONES MEDIATE THE IN-VIVO INHIBITION OF RAT IGE() T)

In the following study, we demonstrate that medium responder PVG rats immunized i.p. with OVA complexed to the adjuvant aluminum hydroxide e xhibit a moderate IgE response (400-1000 ng/ml). In these rats, we dem onstrate that underlying the MHC class Ii-restricted CD4(+) T cell res ponse, there is an MHC class I-restricted CD8(+) T cell component that plays an important role in restricting the magnitude and duration of the IgE response. We show that in vivo depletion of CD8(+) T cells eff ects a massive increase in IgE (20-fold), and that they are MHC class I-restricted, OVA-specific, cytolytic cells that universally produce I FN-gamma (25-69 ng/ml) and IL-2 (7.6-22 U/ml), and occasionally secret e IL-4 (68-81 U/ml IL-4), and when adoptively transferred into CD8-dep leted recipients, can effect a significant reduction in IgE (3- to 50- fold). We also demonstrate that this in vivo inhibition of IgE is depe ndent on the Ag-specific activation of the CD8(+) T cells, and that th e activated CD8(+) T cells will suppress total/bystander IgE in an Ag- nonspecific manner. These data are consistent with a growing literatur e demonstrating sensitization of MHC class I-restricted CD8(+) T cells by exogenous protein Ags delivered to mucosal sites, and may represen t a mechanism whereby a selective pressure can be applied on the funct ional outcome of an immunoglobulin response to environmental allergens .