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Ricin-Sensitive Early Activated CD8+ T Cells Suppress IgE Responses and Regulate the Production of IFN-γ and IL-4 by Splenic CD4+, CD8+ T Cells.

Immunization of rats with a bystander antigen and the toxic lectin, ricin, results in a dramatically potentiated IgE response which was only seen when ricin was administered together with antigen, or 24 h later, suggesting that the toxin was acting on cells which were activated as the result of immunization. The identity of these activated cells was investigated in radioligand bindings studies with 125I ricin. No difference was seen in the number of ricin binding sites on splenic CD4+ and CD8+ T cells from untreated rats, but the number of ricin binding sites was 13-fold higher on CD8+ but not on CD4+ T cells from immunized rats. Adoptive transfer of 1 × 108 >99% pure CD8+ T cells from animals, immunized 3 days before with antigen alone, suppressed the IgE response to antigen plus alum by over 90%. The IgE suppressive effect of these CD8+ T cells was not antigen specific, and they had no effect on the IgG antibody response. CD4+ T cells from none of these animals had any effect on the subsequent IgE of IgG antibody response. The capacity of CD4+ and CD8+ T cells stimulated with PHA or PMA and ionomycin to secrete the cytokines IL-2 and IFN-γ or to make IL-4 mRNA was also compared. CD8+ T cells were the highest producers of IFN-γ and accounted for 65% oftotal splenic IFN-γ. Immunization with ricin plus antigen reduced the amount of IFN-γ secreted by CD4+ (OX22+/--) and CD8+ T cells 5- to 10-fold. Over 95% of the IL-2 produced was derived from OX22+CD4+ T cells, and this did not change. In spleen cells from unimmunized animals, the largest amounts of IL-4 mRNA were found in CD8+ T cells. Following immunization with antigen plus ricin, total splenic IL-4 mRNA production was increased 3- to 4-fold and following boosting with ricin plus antigen was increased a further 3 to 4-fold. These results show: (i) that approximately 50% of splenic CD8+T cells are activated within24h of immunization with antigen, (ii) that adoptive transfer of these cells suppresses IgE production, (iii) that co-administration of ricin and antigen selectively depletes them, (iv) that this is associated with a massive increase in serum IgE a decreased capacity of T cells to produce IFN-γ and an increased capacity to make IL-4. These data suggest that CD8+ T cells, activated early in the immune response, play an important part in regulating cytokine and IgE production.