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Combination therapy to treat type 1 diabetes

Combination therapy to treat type 1 diabetes

PhD project

Antigen-specific therapy to restore immune tolerance has an excellent safety profile but despite its success in allergy, is not yet clinically effective in type 1 diabetes. One of the major hurdles for antigen-specific therapies is that it is difficult to delete antigen-experienced memory T cells. T cell exhaustion, a state of cellular dysfunction induced during chronic antigen exposure, is an important reason for failure of T cells to control tumor progression and chronic viral infection. Conversely, T cell exhaustion has also been linked to favourable long-term clinical outcome in autoimmune disease and it has been associated with the prevention of progression rather than initiation of autoimmune disease. Thus inducing exhaustion of antigen-experienced memory T cells may be a logical next step in preventative therapy in type 1 diabetes. We hypothesise that in type 1 diabetes, ongoing pro-inflammatory signals in the islets (insulitis) inhibit stable T-cell exhaustion. Our preliminary data show that chronic antigen treatment in the presence of insulitis induces partial T cell exhaustion, but the T cells retain the ability to kill target cells. We have also demonstrated that short-term treatment with inhibitors of JAK1/2 significantly reduce insulitis, but on-going treatment is required to maintain this effect. We will test if the combination of these two partially effective therapies can disable pathogenic T cells.

Supervised by:

  • Dr Bala Krishnamurthy
  • Prof Helen Thomas
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Islet biology