| Description: |
Differential activation of CD4 + T cell subsets in vivo leads to the development of qualitatively different effector responses. We identify an approach that allows selective activation of strongly Thl-dominated immune responses to protein antigens. Whereas in vivo administration of ovalbumin (OVA) induces cytokine synthesis that is neither Thl nor Th2 dominated, administration of glutaraldehyde polymerized, high relative molecular weight OVA (OA-POL) leads to 20-fold increase in the ratio of interferon 3 ' (IFN-3")/IL-4 and IFN-3"/IL-10 synthesis observed after shortterm, antigen-mediated restimulation directly ex vivo. In contrast, concurrent in vivo administration of anti-IFN-3/mAb and OVA or OA-POL results in marked increases in IL-4 and IL-10, and decreased IFN-3 ' production, reflecting a polarization of the response towards a Th2-1ike pattern of cytokine synthesis. These observations may be useful in clinical settings including hypersensitivity, autoimmune diseases, and vaccine development where the ability to actively select specific patterns of cytokine gene expression would be advantageous. he pattern of cytokine production elicited after in vivo exposure to antigen largely determines the type of effector immune responses that develop (1-4). Many antigen-driven |