CD8+ T cells inhibit immunoglobulin E synthesis in low responder SJL/J mice

In an effort to examine the basis for low IgE responsiveness of SJL/J strain mice, we analysed the profiles of cytokines, such as interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma), in SJL/J and A.SW/SnJ mice following immunization. Splenocytes of ovalbumin (OVA)-immunized SJL/J mice, secreted significantly higher levels of IL-4 and lower levels of IFN-gamma than those of A.SW/SnJ mice. A time-course analysis of cytokine expression in in vitro cultures of spleen cells indicated that the levels of IL-4 and IL-2 remained persistently high throughout in the cultures of SJL/J splenocytes as opposed to those of A.SW/SnJ. Depletion of CD4+ T cells in vivo suppressed the production of IL-2, IL-4 and IFN-gamma suggesting that CD4 T cells are the producers of most cytokines in both SJL/J and A.SW/SnJ mice. Depletion of CD8+ T cells in vivo not only induced productive epsilon transcript but also enhanced IgE production in SJL/J mice. Moreover, CD8 depletion in SJL/J mice led to decreased production of IFN-gamma, resulting in a net decrease in the ratio of IFN-gamma to IL-4. A similar shift in the IFN-gamma/IL-4 ratio was found in splenocytes of SJL/J mice following irradiation, which is known to enhance IgE synthesis in these mice. Taken together, it is concluded that low IgE responsiveness in SJL/J mice is not due to a defect in IL-4 production per se. Increased IFN-gamma production by the CD8+ T cells inhibits class switch and suppresses IgE antibody production in SJL/J mice.