Long-term incompatible kidney survival in outbred higher primates without chronic immunosuppression

Area of Science:

• Transplantation immunology
• Immunoregulation
• Primate models

Background:

• Chronic immunosuppression (CI) is a major limitation in human allograft transplantation.
• Achieving long-term graft survival without CI remains a significant challenge in the field.

Purpose of the Study:

• To investigate the potential of a novel protocol to induce long-term acceptance of incompatible kidney allografts in nonhuman primates without CI.
• To evaluate the efficacy of rabbit antithymocyte globulin (RATG) combined with donor bone marrow (BM) infusion.

Main Methods:

• Rhesus monkeys received incompatible kidney transplants.
• A 5-day course of RATG was administered, followed by intravenous donor BM infusion on day 12.
• Recipients were monitored for T-cell levels, T-cell subsets, and mixed lymphocyte reaction (MLR) responses.

Main Results:

• Control animals had a mean graft survival of 9.2 days.
• Animals treated with RATG alone rejected grafts by a mean of 35.8 days.
• Four out of five animals receiving RATG and BM survived beyond 150 days (median 248 days), showing prolonged OKT4/OKT8 imbalance and suppressed MLR.

Conclusions:

• The combination of RATG and donor BM induces synergistic immunoregulatory effects, leading to long-term allograft survival in outbred primates without CI.
• This primate model represents a significant advancement, potentially paving the way for CI-free tolerance in human transplantation.