Sign in Subscribe
Universities and colleges

Apoptosis of CD4(+)CD25(high) T cells in response to Sirolimus

Strategic Insights

— 1 min read

Researchers from the University of Virginia have investigated the effects of Sirolimus and Sorafenib on lymphoid cell subsets, revealing that both drugs are cytotoxic to CD4(+)CD25(high) T cells and can induce apoptosis. The study highlights the potential for targeted molecular therapies to affect immune cells, which may impact the efficacy of immunotherapy protocols.

Key Takeaways:

  • Sirolimus and Sorafenib are cytotoxic to CD4(+)CD25(high) T cells, with 80-90% of cells killed by 72 hours.
  • Cell death is due to apoptosis, based on Annexin V and 7AAD staining.
  • Activation of the T cell receptor is required for the cytotoxic effects of Sirolimus.
  • Addition of IL-2 prevents the apoptotic response to Sirolimus.
  • The study suggests that IL-2 may be used to protect CD4(+)CD25(high) T cells from cytotoxic effects of Sirolimus.
  • The researchers concluded that administration of IL-2 protects CD4(+)CD25(high) T cells from cytotoxic effects of Sirolimus.
  • The study has implications for designing therapeutic protocols, particularly in immunotherapy.
  • The researchers noted that Sirolimus can enhance proliferation of CD4(+)CD25(high) cells, which may be related to its effects on immune cells.
  • The study suggests that Sirolimus or Sorafenib would reduce CD4(+)CD25(high) cells if administered prior to antigenic stimulation in an immunotherapy protocol.

Statistics:

  • 80-90% of CD4(+)CD25(high) cells are killed by Sirolimus within 72 hours.
  • Cytotoxicity to CD4(+)CD25(high) T cells is detectable within 12 hours in response to CD3/CD28 stimulation.
  • The study involved examination of the effects of Sirolimus and Sorafenib on proliferation and survival of lymphoid cell subsets.
  • The researchers evaluated the effects of both drugs on CD4(+) and CD8(+) T cells.
  • IL-2 prevents the apoptotic response to Sirolimus, with 80-90% of cells killed by 72 hours.

Sources:

  • Molhoek, K.R., et al. "Apoptosis of CD4(+)CD25(high) T cells in response to Sirolimus requires activation of T cell receptor and is modulated by IL-2." Cancer Immunology, Immunotherapy 58.6 (2009): 867-76.
  • Cancer Immunology, Immunotherapy, 2009;58(6):867-76.
  • University of Virginia School of Medicine, University of Virginia School of Medicine, Dept. of Surgery, Charlottesville, VA 22908 USA.
  • Springer, 233 Spring Street, New York, NY 10013, USA.

Read more