IMPAIRED CD28-MEDIATED CO-STIMULATION IN ANERGIC T-CELLS

We have investigated a CD28 co-stimulation in anergic T cells in staph ylococcal enterotoxin B-inoculated mice by stimulating the cells with a plate-coated anti-TCR antibody in the presence or absence of an anti -CD28 antibody. CD28 co-stimulation increased the levels of IL-2 and I L-4 mRNAs in naive CD4(+)V(beta)8(+) T cells. However, it did not incr ease the levels of IL-4 mRNA at all and only partially increased those of IL-2 mRNA in anergic T cells. It was demonstrated that CD28 co-sti mulation was impaired so that it no longer stabilized cytokine mRNAs i n anergic cells. The levels of IL-4 mRNA in response to TCR stimulatio n were higher in anergic T cells than those in naive T cells in spite of the defective CD28 co-stimulation in the former cells. Anergy induc tion and generation of a T(h)2-type immune response in vivo are discus sed.