Uncoupling of cytokine mRNA expression and protein secretion during the induction phase of T cell anergy

The CD4⁺ T cell clone HA1.7 may be made specifically nonresponsive, or anergic, to its cognate Ag, an influenza hemagglutinin peptide (HA), by preteatment with the superantigen Staphylococcus aureus enterotoxin B or with high concentrations of HA itself. We compare the patterns of mRNA expression and protein production of selected T cell cytokines during the first 24 h after treatments that induce anergy in HA1.7 and during the same period after treatments that simulate normal cellular activation. The cytokines examined include TNF-α, IL-8/neutrophil activating protein-1 and the RANTES/ SIS cytokines, a family of small secreted proteins with inflammatory and potential antiproliferative and leukocyte regulating activities. Messenger RNA for TNF-α, human MIP-1α, human MIP-1β, and IL-8 are all induced during the development of clonal anergy in HA1.7, and these levels are significantly higher than those seen during activation of the clone using an anti-CD3 antibody and IL-2. These high levels of mRNA also persist longer than those seen after anti-CD3 and IL-2 activation. However, the increased levels of mRNA are not typically accompanied by increased protein secretion. In all cases but one, the amount of cytokine secreted by HA1.7 cells was greater after anti-CD3 and IL-2 treatments than after anergy- inducing treatments. Thus, the induction of T cell anergy in HA1.7 does not appear to require a general inhibition of T cell cytokine mRNA expression, and, in fact, anergy treatments appear to superinduce certain cytokine transcripts, but anergy-specific posttranscriptional mechanisms may exist by which cytokine release is regulated.