Cytotoxic T Lymphocyte-associated Protein 4 Acts on Local Draining Lymph Nodes in the Allogeneic Abdominal Skin Flap of a Rat Model to Extend Its Survival.

BACKGROUND: Early acute allograft rejection is the result of immune cells mainly composed of thymocyte (T) cells, which are activated, mature, and differentiate in lymphoid tissue.

METHODS: Cytotoxic T lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) competitively suppresses the cluster of differentiation 28/CTLA4-B7 costimulatory signaling pathway and alters the ratio of T helper 1 to T helper 2, leading to the inhibition of T cell activation.

RESULTS: We used lentivirus-packed CTLA4-Ig to infect the local draining lymph nodes of the allograft skin flap in a rat model, which effectively extended the survival of the allograft. Meanwhile, it also reduced the dose of immunosuppressant necessary in the early stages of transplantation, which lowered the toxicity and side effects of the drug.

CONCLUSIONS: Our findings provide new insights into transplantation immunology, facilitate the exploration of a safe and effective immunosuppressive therapy, and promote the wide clinical application of composite tissue allotransplantation.