Antigen-specific CD8(+) T cells inhibit IgE responses and interleukin-4 production by CD4(+) T cells

There is a growing body of evidence which suggests that CD8(+) T cells play an important part in regulating the IgE response to non-replicating antigens. In this study we have systematically investigated their role in the regulation of IgE and of CD4(+) T cell responses to ovalbumin (OVA) by CD8(+) T cell depletion in vivo. Following intraperitoneal immunization with alum-precipitated OVA, OVA-specific T cell responses were detected in the spleen and depletion of CD8(+) T cells in vitro 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 greatly enhanced the IgE response, which rose to 26 mu g/ml following a second 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-depleted on day 12 with purified CD8(+) T cells from animals immunized on day 12. completely inhibited the IgE response. This effect was antigen specific; CD8(+) T cells from OVA-primed animals had little effect on the IgE response of bovine serum albumin immunized rats. In vivo, CD8(+) T cell depletion decreased interferon (IFN)-gamma production but enhanced 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-supplemented mixed lymphocyte reaction. These data clearly show chat antigen-specific CD8(+) T cells inhibit IgE in the immune response to non-replicating 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.