ANTIGEN-SPECIFIC CD8(-CELLS INHIBIT IGE RESPONSES AND INTERLEUKIN-4 PRODUCTION BY CD4(+) T-CELLS() T)

There is a growing body of evidence which suggests that CD8(+) T cells play an important part in regulating the IgE response to non-replicat ing antigens. In this study we have systematically investigated their role in the regulation of IgE and of CD4(+) T cell responses to ovalbu min (OVA) by CD8(+) T cell depletion in vivo. Following intraperitonea l immunization with alum-precipitated OVA, OVA-specific T cell respons es were detected in the spleen and depletion of CD8(+) T cells in vitr o significantly enhanced the proliferative response to OVA. Depletion of CD8(+) T cells in vivo 7 days after immunization failed to enhance IgE production, while depletion of CD8(+) T cells on days 12-18 greatl y enhanced the IgE response, which rose to 26 mu g/ml following a seco nd injection of anti-CD8 on day 35 and remained in excess of 1 mu g/ml over 300 days afterwards. Reconstitution on day 21 of rats CD8-deplet ed on day 12 with purified CD8(+) T cells from animals immunized on da y 12. completely inhibited the IgE response. This effect was antigen s pecific; CD8(+) T cells from OVA-primed animals had little effect on t he IgE response of bovine serum albumin immunized rats. In vivo, CD8() T cell depletion decreased interferon (IFN)-gamma production but enh anced interleukin (IL)-4 production by OVA-stimulated splenic CD4(+) T cells. Furthermore, CD8(+) T cell depletion and addition of anti-IFN- gamma antibody enhanced IgE production in vitro in an IL-4-supplemente d mixed lymphocyte reaction. These data clearly show chat antigen-spec ific CD8(+) T cells inhibit IgE in the immune response to non-replicat ing antigens. The data indicate two possible mechanisms: first, CD8(+) T cells have direct inhibitory effects on switching to IgE in B cells and second, they inhibit OVA-specific IL-4 production but enhance IFN -gamma production by CD4(+) T cells.