Regulatory T cells – Maizels Lab

Studies from the Maizels Lab and others have established the prominent role of regulatory T cells (Tregs) in facilitating and maintaining helminth infections. Our most recent review by McManus and Maizels (2023) is here.

Key advances in the field from our lab have been:

In vivo role of Tregs:

Tregs expand in H. polygyrus infection in mice (Finney et al, 2008), and depletion of Tregs renders mice resistant (Smith et al., 2016). In filarial nematode infection, Brugia malayi also expands TYregs (McSorley et al 2008), while in infection with Litomosoides sigmodontis, combination treatment with anti-CD25 with anti-CTLA-4 or anti-GITR elicits parasite killing (Taylor et al 2005, 2007). Tregs also mediate bystander suppression of allergy in mice (Wilson et al 2005).

Treg expansion driven by parasite products: H. polygyrus ES induces the canonical Treg transcription factor Foxp3 in naive T cells, phenocopying TGF-β (Grainger et al 2010).

HES contains a family of TGF-β mimics (TGMs) described here.

Tregs are now understood to play an integral role in most parasitic diseases, but can act to facilitate infection and/or protect against pathological outcomes, depending on the host/parasite combination (McManus and Maizels 2023)

References

Finney, C.A.M., Taylor, M.D., Wilson, M.S. and Maizels, R.M. (2007) Expansion and activation of CD4⁺CD25⁺ regulatory T cells in Heligmosomoides polygyrus infection. European Journal of Immunology 37 : 1874-1886

Grainger, J.R., Smith, K.A., Hewitson, J.P., McSorley, H.J., Harcus, Y., Filbey, K.J., Finney, C.A.M., Greenwood, E.J.D., Knox, D.P., Wilson, M.S., Belkaid, Y., Rudensky, A.Y., and Maizels, R.M. (2010) Helminth secretions induce de novo T cell Foxp3⁺expression and regulatory function through the TGF-β pathway. Journal of Experimental Medicine 207: 2331-2341

McManus, C. and Maizels, R.M. (2023) Regulatory T cells in Parasite Infections: Susceptibility, Specificity and Specialisation. Trends in Parasitology 39: 547-562. doi : 10.1016/j.pt.2023.04.002

McSorley, H., Harcus, Y., Murray, J., Taylor, M.D. and Maizels, R.M. (2008) Expansion of Foxp3⁺ regulatory T cells in mice infected with the filarial parasite, Brugia malayi. Journal of Immunology 181: 6456-6466

Taylor, M.D., LeGoff, L., Harris, A., Malone, E., Allen, J.E. and Maizels, R.M. (2005) Removal of regulatory T cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo. Journal of Immunology 175 : 4924-4933

Taylor, M.D., Harris, A., Babayan, S., Bain, O., Allen, J.E. and Maizels, R.M. (2007) CTLA-4 and CD4⁺CD25⁺regulatory T cells inhibit protective immunity to filarial parasites in vivo. Journal of Immunology, 179 : 4626-4634

Wilson, M S., Taylor, M., Balic, A., Finney, C.A.M., Lamb, J.R. and Maizels, R.M. (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. Journal of Experimental Medicine 202: 1199-1212.