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

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Abstract
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 μ/ml following a second injection of anti‐CD8 on day 35 and remained in excess of 1 μ/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 inhib ited 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)‐γ production but enhanced interleukin (IL)‐4 production by OVA‐stimulated splenic CD4+ T cells. Furthermore, CD8+ T cell depletion and addition of anti‐IFN‐γ antibody enhanced IgE production in vitro in an IL‐4‐supplemented mixed lymphocyte reaction. These data clearly show that 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‐γ production by CD4+ T cells.