The origins of the adaptive immune system and the basis for its unique association with vertebrate species have been a source of considerable speculation. In light of recent advances in our understanding of the developmental and functional links between the induced regulatory T cell and T helper 17 cell lineages, and their specialized relationship to the gut, we speculate that the co-evolution of these adaptive immune pathways might have given primitive vertebrates a means to benefit from the diversification of their commensal microbiota.

Regulatory T (T) cells suppress inflammation and regulate immune system activity. In patients with systemic or organ-specific autoimmune diseases or those receiving transplanted organs, T cells are compromised. Approaches to strengthen T cell function, either by expanding them ex vivo and reinfusing them or by increasing the number or capacity of existing T cells, have entered clinical trials. Unlike the situation in autoimmunity, in patients with cancer, T cells limit the antitumour immune response and promote angiogenesis and tumour growth. Their immunosuppressive function may, in part, explain the failure of many immunotherapies in cancer. Strategies to reduce the function and/or number of T cells specifically in tumour sites are being investigated to promote antitumour immunity and regression. Here, we describe the current progress in modulating T cells in autoimmune disorders, transplantation and cancer.