CD8(-CELLS INHIBIT IMMUNOGLOBULIN-E SYNTHESIS IN LOW RESPONDER SJL() T)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 interleuki n-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma), in SJL/J and A.SW/S nJ mice following immunization. Splenocytes of ovalbumin (OVA)-immuniz ed 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 analysi s of cytokine expression in in vitro cultures of spleen cells indicate d that the levels of IL-4 and IL-2 remained persistently high througho ut in the cultures of SJL/J splenocytes as opposed to those of A.SW/Sn J. 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 o f most cytokines in both SJL/J and A.SW/SnJ mice. Depletion of CD8(+) T cells in vitro not only induced productive epsilon transcript but al so enhanced IgE production in SJL/J mice. Moreover, CD8 depletion in S JL/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 IF N-gamma/IL-4 ratio was found in splenocytes of SJL/J mice following ir radiation, which is known to enhance IgE synthesis in these mice, Take n 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.