Cytokine gene expression of CD8+ suppressor T cells induced by tolerogenic conjugates of antigen and mPEG

Abstract

Nonhybridized CD8+ Ts cell clones were generated from individual spleen cells of a B6D2F1 mouse, which had been immunosuppressed in an antigen-specific manner by administration of tolerogenic conjugates of ovalbumin (OVA) and monomethoxypolyethylene glycol. The cloned Ts cells were shown to suppress both in vivo and in vitro anti-OVA antibody formation in an antigen-specific and isotype-nonspecific manner, i.e., IgM, IgG1, and IgG2a anti-OVA antibodies were suppressed. The cytokine profile of three Ts cell clones was determined by bioassays, Western blot, and polymerase chain reaction analyses. It was shown that all the Ts cell clones produced IL-2, IL-4, IFN-gamma, TGF-beta 1, LT, and TNF-alpha upon activation with hamster anti-CD3 monoclonal antibody (mAb) or antigen plus APC. However, neither the mAbs to IFN-gamma, TGF-beta, or LT/TNF-alpha, nor the recombinant IL-2 was able to abrogate the suppression of in vitro antibody production by cloned Ts cells. These data are taken to indicate that (i) the cloned Ts cells suppress anti-OVA antibody production both in vivo and in vitro in an isotype-nonrestricted manner, (ii) the cytokine profile of these cloned Ts cells is similar to that of Th0 cells, and (iii) the immunosuppression mediated by these T cells is not directly related to the cytokines produced by cloned Ts cells.