Tetanus Toxoid

Tetanus is a potentially fatal condition. In developing and poor countries where vaccination rates can be low, tetanus is still a substantial public health concern. Researchers showed that tetanus toxoid (TT) can interact with γδ T cells, which may offer a novel direction for the tetanus study.

Introduction of Tetanus Toxoid

Tetanus is a vaccine-preventable disease that is caused by a potent neurotoxin produced by the spore-forming bacterium Clostridium tetani. The spores of C. tetani are present in the environment throughout the world and can contaminate wounds, minor abrasions, and, in neonatal tetanus, the umbilical stump. In anaerobic conditions, the spores of C. tetani produce vegetative bacteria, which express the tetanus toxin and cause the disease. The tetanus vaccine, also known as tetanus toxoid (TT), is inactive used to prevent tetanus. The advent of the vaccine resulted in a further reduction in high-income countries and also opened opportunities for progress in low-income settings. Tetanus affects all mammals, although susceptibility to the disease is variable. In humans, the disease remains common in many low-income and middle-income countries and, although rare in developed settings, it still presents a substantial diagnostic and therapeutic challenge. Tetanus is prevented through vaccination with TT, but because the causative agent is widespread in the environment, eradication is impossible. Therefore, efforts to reduce incidence are aimed at reaching elimination, rather than eradication.

Fig.1 Acridine orange stain of characteristic C. tetani with endospores wider than the characteristic drumstick shape. (Farrar, 2000)

Tetanus Toxoid and γδ T Cells

Researchers have analyzed the ability of human γ⁺/δ⁺ T cells to recognize a nominal antigen in association with MHC molecules. A TT specific T cell line with 40% γ⁺/δ⁺ T cells was established from a hyper immunized donor, D.E, by stimulation with antigen and autologous APC. Three DF derived γ⁺/δ⁺ clones were CD8⁺ as determined by immunofluorescence staining, and by Southern and Northern blotting with probes detecting δ chain rearrangement and δ and γ chain transcripts, respectively. The γ⁺/δ⁺ clones responded to stimulation with TT, but not TNP-BSA, and autologous APC by proliferation and IFN-γ production. No proliferation or IFN-γ production was detected when TT-specific T cell clones were stimulated with either TT or autologous APC only. The response to TT was enhanced by the addition of exogenous IL-2. The use of allogeneic APC from 19 donors sharing one HLA determinant with the autologous donor D.E, showed that the γ⁺/δ⁺ T cells responded to TT with HLA-DR4-related restriction as measured by proliferation and IFN-γ production. These results demonstrate that γ/δ receptors can recognize non-MHC-encoded foreign antigen in a self-MHC-restricted fashion.

Indeed, it has been reported that short-term activated γδ T cells were capable of processing simple (TT) and complex (M. tuberculosis PPD) protein antigens and inducing antigen-specific immune responses in primary, autologous αβ T cells. However, there are still many gaps in this field. Therefore, it is necessary to further study how to utilize the interaction of γδ T cells and TT.

Reference

1. Farrar, J. J.; et al. Tetanus. J Neurol Neurosurg Psychiatry. 2000, 69(3): 292-301.