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Total lymphoid irradiation.

D E Sutherland, R M Ferguson, R L Simmons

    The Urologic Clinics of North America
    |May 1, 1983
    PubMed
    Summary
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    Total lymphoid irradiation (TLI) can prolong organ transplant survival in animals by suppressing the immune system. Its clinical use for tolerance induction faces challenges like graft-versus-host disease and competition with current immunosuppression methods.

    Area of Science:

    • Immunology
    • Transplantation Medicine
    • Radiation Oncology

    Background:

    • Total lymphoid irradiation (TLI) demonstrates significant immunosuppressive capabilities in experimental models, prolonging allograft survival.
    • TLI's effectiveness is dose-dependent, with higher doses leading to toxicity, and it is generally more effective when administered before transplantation.
    • While TLI can induce tolerance through bone marrow engraftment and chimerism in some animal models, graft-versus-host disease is a concern.

    Purpose of the Study:

    • To evaluate the potential of Total lymphoid irradiation (TLI) as an immunosuppressive agent in organ transplantation.
    • To explore TLI's capacity to induce long-term tolerance to allografts, potentially eliminating the need for maintenance immunosuppression.
    • To assess the feasibility of TLI in clinical transplantation, considering its efficacy and toxicity compared to existing treatments.

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    Main Methods:

    • Review of experimental animal studies investigating the effects of Total lymphoid irradiation on organ allograft survival and immune tolerance.
    • Analysis of TLI's efficacy in combination with pharmacologic immunosuppression post-transplantation.
    • Examination of TLI-induced bone marrow transplantation protocols leading to permanent chimerism and donor-specific tolerance.

    Main Results:

    • Total lymphoid irradiation (TLI) effectively prolongs allograft survival in a dose-dependent manner, limited by toxicity at higher doses.
    • TLI can facilitate bone marrow engraftment and induce tolerance to organ allografts in animal models, but graft-versus-host disease is a potential complication.
    • Current patient and graft survival rates with cyclosporine and conventional immunosuppression in renal transplantation are high, making TLI's sole use less compelling for primary transplants.

    Conclusions:

    • Total lymphoid irradiation (TLI) shows promise for inducing immune tolerance in transplantation, particularly in animal models.
    • Clinical application of TLI may require strategies to mitigate graft-versus-host disease and enhance its efficacy.
    • The future of TLI in transplantation likely involves developing protocols to eliminate or reduce maintenance immunosuppression, though clinical applicability remains to be determined.