The sensitivity of rat CD8+ and CD4+ T cells to ricin in vivo and in vitro and their relationship to IgE regulation.

In a previous paper we described how the toxin ricin stimulates IgE but not IgG antibody responses in rats. In this study we have examined the cellular basis for this observation. The proportion of CD4- and CD8-positive cells present in the spleen at the peak of the IgE response was determined. Those animals injected with both ricin and antigen produced a substantial IgE response (50-fold increase). Their CD4+/CD8+ ratio was also markedly increased (P less than 0.001) compared with animals given toxin or antigen alone. In addition, mitogen-stimulated proliferation of mononuclear cells from spleens of the IgE-producing rats was enhanced nearly five-fold compared with cells from animals given toxin or allergen alone. The sensitivity of CD4- and CD8-positive rat spleen cells from unexposed animals to ricin in vitro was also studied. Spleen cells from untreated rats were co-cultured with optimal doses of mitogen and varying amounts of ricin. Mitogen-driven proliferation was inhibited at 10(-3) - 10(-6) mg/ml ricin. This effect was abrogated by the addition of as little as 0.01 M lactose but not by as much as 10 mg/ml mannan to the culture. Cultures depleted of CD4+ cells by rosetting were approximately 100 times more sensitive to ricin (P less than 0.01). Furthermore, the proportion of CD8+ to CD4+ cells present after culture of untreated cells with mitogen and ricin was significantly reduced. These results show (i) that the ability of ricin to increase the IgE response depends on the administration of antigen together with the toxin; (ii) that CD8+ spleen cells are more sensitive to ricin than CD4+ cells; (iii) that increased IgE responsiveness is associated with a reduction in the proportion of CD8- relative to CD4-positive cells in the spleen and increased responsiveness to mitogen. We believe that enhancement of the IgE responses by ricin may be due to inactivation of IgE-specific T-suppressor cells generated by immunization with antigen and speculate that these may be some or all of those bearing the CD8 marker.