Tetanus neurotoxin H-CC protein commits T cells to IFN-gamma producing cells

Abstract

A protective response against tetanus toxin and toxoid demands efficient specific T cell and B cell responses. Tetanus neurotoxin (TeNT), a 150 kDa polypeptide, is the main cause of tetanus disease. TeNT consists of two structurally distinct chains, a 50 kDa N-terminal light (L) and a 100 kDa C-terminal heavy (H) chain. C-terminal heavy (H) chain (fragment C) has two sub-domains named as proximal H-CN and carboxy sub-domain or H-CC. Beside neural binding property, H-CC has been recently found as an immunodominant module of TeNT. In the present study, we investigated the effects of recombinant H-CC (rH(CC)) on the expression of lineage specific transcription factors and secretion of a panel of functional cytokines including IFN-gamma, IL-4, and IL-17 from purified human T cells. Our results revealed that T-bet transcript level, as TH1 specific transcription factor, was significantly increased in the cells treated with 10 and 20 mu g/ml of rH(CC) following 48 h treatment(p<0.05). Treated purified human T cells with rH(CC) showed significant increase in IFN-gamma mRNA level and cytokine secretion, but not IL-4 and IL-17, following 48 h treatment. In conclusion, our results showed that treatment of T cells with r H-CC resulted in development of Th1 lineage phenotype, which might lead to a specific and protective antibody mediated response against tetanus toxin.