Total lymphoid irradiation in alloimmunity and autoimmunity

Area of Science:

• Immunology
• Radiotherapy
• Transplantation Medicine

Background:

• Total lymphoid irradiation (TLI) is an established immunosuppressive regimen used in autoimmune disease and organ transplantation.
• Its use is based on observations in Hodgkin disease patients, where TLI induced significant, durable immune suppression with minimal side effects.
• TLI selectively reduces helper T cells and certain B cell subsets, offering a targeted approach compared to conventional immunosuppressants.

Purpose of the Study:

• To explore the potential of Total lymphoid irradiation (TLI) in achieving long-term immune tolerance in transplantation.
• To investigate TLI's efficacy in inducing permanent remissions for autoimmune diseases.
• To assess the feasibility of withdrawing immunosuppressive drugs in transplant recipients and lupus nephritis patients treated with TLI.

Main Methods:

• Utilizing Total lymphoid irradiation (TLI) as a radiotherapy-based immunosuppressive strategy.
• Evaluating the long-lasting effects of TLI on immune cell populations, specifically helper T cells and B cells.
• Observing outcomes in laboratory animals to determine the potential for transplantation tolerance and autoimmune disease remission.

Main Results:

• TLI demonstrated a selective and long-lasting reduction in the number and function of helper T cells and specific B cell subsets.
• In laboratory animals, TLI showed significant potential for inducing transplantation tolerance.
• TLI exhibited promise for achieving permanent remissions in autoimmune diseases in animal models.

Conclusions:

• Total lymphoid irradiation (TLI) presents a unique, selective, and long-lasting immunosuppressive modality.
• TLI holds potential for inducing transplantation tolerance and achieving durable autoimmune disease remission, surpassing conventional immunosuppressive drugs.
• Ongoing human trials aim to leverage TLI to enable the discontinuation of immunosuppressive drugs in transplant recipients and patients with conditions like lupus nephritis.