Authors
Pathak, S., Ahmed, R., Nagy, N., Lee, S., Bader, C., Regmi, S., Iliopoulou, B., Chen, P., Gupta, B., Villar-Prados, A., Kim, Y. B., Hussein, N., Soohoo, E., Twoy, A., Thakor, A., Jensen, K., Utz, P., Davis, M. M., Annes, J., Meyer, E.
Abstract
Type 1 diabetes (T1D) is caused by T cell-mediated autoimmune destruction of insulin-producing islet beta-cells. Treatment with T-cell depleting therapies delays the progression of stage 2 and 3 T1D, but these agents exert broad immunosuppressive effects on T cell populations, including T regulatory cells (Tregs), which are key in promoting immune tolerance. We evaluated non-obese diabetic (NOD) mice and recently diagnosed T1D patients and identified CD38 as a marker for pathogenic T cell populations. Using adoptive T-cell transfer in Recombination Activating Gene 1 knockout NOD mice and in a humanized mouse model of autoimmune diabetes, we demonstrated that CD38-expressing autoreactive T cells drive diabetes pathogenesis. Furthermore, we found that selective depletion of CD38+ cells, using an anti-CD38 monoclonal antibody (mAb), prevents insulitis and diabetes onset without depleting CD4+CD25+ Tregs. Administration of anti-CD38 mAb did not adversely affect islet function and may selectively eliminate immunogenic senescent islet beta-cells. These results support the strategy of selectively depleting diabetogenic T cells using an anti-CD38 mAb to treat T1D and restore immune tolerance. Therefore, transient depletion of autoreactive T cells using anti-CD38 mAb may provide a novel strategy to prevent or abrogate autoimmunity in T1D.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 02 Jul 2026.
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