THE ROLE OF CD8(+) CELLS IN THE REGULATIO N OF IGE

The link between IgE antibodies to environmental allergens, allergic s ensitization and atopic diseases such as asthma, rhinitis and eczema i s well established, yet treatment of these diseases is largely symptom atic and fails to correct the underlying immunological disorder. B cel l production of IgE is dependent on IL-4 and is inhibited by IFN-gamma . These cytokines are produced by T-helper 2 (Th2) and T-helper 1 (Th1 ) CD4(+) T cells, respectively. In atopic dermatitis skin and asthmati c lung, Th2 cells predominate. There is an increasing body of evidence to indicate that CD8(+) T cells play an important role in determining the direction (cytotoxicity versus hypersensitivity) that the immune response will take. We have investigated the ability of CD8(+) T cells to synthesize and secrete cytokines before and after culture with IL- 4 and anti-IFN-gamma. Purified rat splenic CD8(+) and CD4(+) T cells a nd CD4(-)CD8(-) cells were stimulated with phorbol myristate acetate ( PMA) and ionomycin for 6 hours and expression of mRNA for IL-2, IL-4, IL-5, IL-6, IL-10 and IFN-gamma determined using a quantitative PCR te chnique. Secreted IFN-gamma and IL-2 were measured by ELISA and bioass ay, respectively, 24 hours after restimulation. The highest levels of IL-4,IL-5 and IFN-gamma mRNA were expressed by CD8(+) T cells, the hig hest levels of message for IL-2 was expressed by CD4(+) T cells and th e highest levels of message for IL-6 and IL-10 by CD4(-)CD8(-) splenoc ytes. Purified rat splenic CD8(+) T cells were cultured for 6 days wit h PMA, ionomycin and IL-2 with or without IL-4 or anti-IFN-gamma and r e-stimulated with PMA and ionomycin. Those CD8(+) T cells cultured wit h IL-4 expressed increased levels of IL-4, IL-5 and reduced levels of IL-2 and IL-6 mRNA, while CD8(+) T cells cultured with IL-4 and anti-I FN-gamma expressed increased levels of mRNA for IL-10 and IFN-gamma. C omparable effects were seen for secreted IFN-gamma and IL-2. These res ults indicate that CD8(+) T cells have the potential to produce large amounts of Th2 cytokines and are able to differentiate into different subpopulations with distinct cytokine profiles under the control of IL -4 and IFN-gamma.